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Developments in CRISPR Patent Dispute: EPO Revokes Broad’s CRISPR Patent, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Developments in CRISPR Patent Dispute: EPO Revokes Broad’s CRISPR Patent

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 1/17/2020

On Thursday, [1/16/2020] the EPO appeals board indicated that it planned to refer the issue to an Enlarged Board of Appeals to decide three questions: whether a European patent application can be refused if it claims the same subject matter as a European patent which was granted to the same applicant and does not form part of the state of the art pursuant to relevant articles of European law; what the conditions for such a refusal could be, and how those conditions should be applied depending on certain filing details in the patent in question; and whether an applicant has a legitimate interest in the grant of a patent on the subsequent European patent application in view of the fact that the filing date and not the priority date is the relevant date for calculating the term of the European patent.

A day later, however, the appeals board reversed its decision to send the case to the enlarged board, and made the decision itself, ruling that the initial revocation of the patent for lack of novelty “in view of immediate prior art” was correct.

“This prior art became relevant because the opposition division did not acknowledge the patentee’s claim to priority from a US provisional application naming more applicants than the subsequent PCT application from which EP 2771468 is derived,” the appeals board wrote in its brief decision. “Since the omitted applicant had not transferred his rights to the applicants of the PCT application the priority claim was considered invalid.”

In a statement, the Broad once again noted that the EPO’s decision doesn’t involve the actual scientific merits of the patent application, but concerns the interpretation of rules that dictate what happens when the names of inventors differ across international applications. The institute noted that up to nine of its 21 CRISPR-Cas9 patents in Europe could be affected by the decision if the EPO doesn’t “harmonize” these requirements, but added that the majority of its patents in Europe will not be affected.

“These include the fundamental claims in EP 2825654B1, as well as others covering certain key therapeutic indications — including for previously untreatable diseases,” the institute said. “In addition, Broad has numerous other CRISPR-Cas9 patent applications pending in Europe that are not affected by this formalities issue, as well as granted and pending patents related to CRISPR-Cas12/Cpf1, which are not affected.”

The Broad also urged all CRISPR patent holders to “move beyond litigation,” and instead work together to ensure that there is wide, open access to the technology.

In a statement on the decision, ERS Genomics CEO Eric Rhodes said the company is “pleased” to see the appeals board’s confirmation of the earlier revocation, adding, To have the issue resolved finally provides some measure of clarity to those companies interested in using and commercializing CRISPR-Cas9 technology. Today’s ruling significantly reduces Broad’s CRISPR-Cas9 patent footprint in Europe and should make licensing decisions much easier for those looking to utilize CRISPR-Cas9 technology in Europe.”

Rhodes also noted to GenomeWeb that the Broad’s call for the parties to put litigation aside and make their technology widely available is an admirable goal, but also a complicated one.

ERS was founded to provide access to CRISPR-Cas9 intellectual property held by Emmanuelle Charpentier. This CRISPR IP is shared between her, Jennifer Doudna and the University of California, and the University of Vienna, and is separate from genome editing patents held by the Broad.

Rhodes noted that the company does make its own CRISPR IP widely available through licensing and other avenues, and although it would be better to have the IP held by the Broad and ERS available through only one source, “it’s a complicated situation.” Both sides involve multiple institutions and companies, making anything involving the pooling of patents a “complex logistical issue,” Rhodes added. There’s a willingness on both sides, but making it happen will be difficult.

SOURCE

https://www.genomeweb.com/business-news/revocation-broad-institute-crispr-patent-upheld-europe#.XiI1V1NKgcg

Other sources

Dublin-based ERS Genomics was founded to provide access to CRISPRCas9 intellectual property held by Emmanuelle Charpentier. This CRISPR IP is shared between her, Jennifer Doudna and the University of California, and the University of Vienna, and is separate from genome editing patents held by the Broad Institute.4 days ago

ERS Genomics Licenses CRISPR-Cas9 IP to Daiichi Sankyo …


https://www.genomeweb.com › business-news › ers-genomics-licenses-crispr…

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ERS Genomics Licenses CRISPR-Cas9 IP to Daiichi Sankyo …


https://www.genomeweb.com › business-news › ers-genomics-licenses-cris…

4 days ago – Dublin-based ERS Genomics was founded to provide access to CRISPRCas9 intellectual property held by Emmanuelle Charpentier. This CRISPR IP is shared between her, Jennifer Doudna and the University of California, and the University of Vienna, and is separate from genome editing patents held by the Broad Institute.

About ERS | ERS Genomics


ERS Genomics was formed to provide broad access to the foundational CRISPRCas9 intellectual property held by co-inventor and co-owner Dr. Emmanuelle …

ERS Genomics Licenses CRISPR Gene Editing Technology to …


https://www.businesswire.com › news › home › ERS-Genomics-Licenses-C…
5 days ago – DUBLIN–(BUSINESS WIRE)–ERS Genomics Limited, which was formed to provide broad access to the foundational CRISPR/Cas9 intellectual property co-owned by Dr. Emmanuelle Charpentier, today announced the signing of a license agreement with Daiichi Sankyo, a global pharmaceutical …

ERS Genomics Announces Agreement With New England …

https://www.biospace.com › article › releases › ers-genomics-announces-ag…
Jan 7, 2020 – BUSINESS WIRE)– ERS Genomics Limited, which was formed to provide broad access to the foundational CRISPR/Cas9 intellectual property …

ERS Genomics Licenses CRISPR Gene Editing Technology to …


https://finance.yahoo.com › news › ers-genomics-licenses-crispr-gene-095…
5 days ago – ERS Genomics Limited, which was formed to provide broad access to the foundational CRISPR/Cas9 intellectual property co-owned by Dr.

CRISPR Therapeutics, Intellia Therapeutics, Caribou …


CRISPR/Cas9 is a revolutionary technology that allows for precise, directed changes … ERS Genomics was formed to provide broad access to the foundational …

ERS Genomics | LinkedIn

Mixed views on Broad’s fate after EPO revokes CRISPR patent

https://www.lifesciencesipreview.com/news/mixed-views-on-broad-s-fate-after-epo-revokes-crispr-patent-2671

 

EPO Revokes Broad’s CRISPR Patent

The Broad Institute of MIT and Harvard University is at risk of losing its dominant position over the intellectual property covering CRISPR gene-editing technology in Europe, after the European Patent Office (EPO) ruled today (January 17, 2018) that a foundational patent is revoked because the Broad did not meet EPO requirements to establish that its researchers were the first to use CRISPR in eukaryotes.

In addition to the highly publicized patent dispute between the Broad and the University of California over the rights to CRISPR gene editing in the U.S., the Broad has been fighting to maintain a number of patents over the technology in Europe. The issue revolves around a disagreement between the Broad and Rockefeller University over who should be named as inventors. The majority of patent applications filed by the Broad in Europe failed to name Rockefeller University itself, as well as Rockefeller researcher Luciano Marraffini, both of which were named on several of the documents filed to establish a priority date for the patent as early as December 2012. Changing the listed inventors goes against the EPO’s formal requirements for priority, leading the agency to rule this morning that the priority documents with the full list of inventors did not count toward establishing priority of the more-limited European filings.

“If you’ve got more than one person on a priority document, they are a singular legal unity,” explains Catherine Coombes, a senior patent attorney with HGF Limited in the U.K. “If you’re going to drop numbers . . . you need to transfer priority from everybody on the first.” Given the ongoing arbitration between the Broad and Rockefeller, it’s not surprising that the Broad did not procure this transfer, she adds.

Today’s decision is the first opposition heard in Europe, but at least 10 other Broad patents have been challenged, many of which have the same issue of leaving out certain inventors from those listed on the documents filed to establish priority. The EPO had put those other proceedings on hold while it looked into this first patent, Coombes says, but now it can apply its ruling to the other cases. “What we will expect to see over the next year or so is a number of the other Broad’s patents in Europe either being completely revoked or being severely limited in Europe.”

The Broad has announced that it will be appealing the EPO’s decision, but “I personally think it’s unlikely that we’ll see a change in direction,” Coombes says. She adds, however, that the institution does have one patent application that does name Rockefeller and Marraffini. “What I would suspect their patent attorneys would be doing is looking over the patent that doesn’t have this [priority] issue and trying to get more claims in that one.”

SOURCE

https://www.the-scientist.com/?articles.view/articleNo/51395/title/EPO-Revokes-Broad-s-CRISPR-Patent/

PRESS RELEASES / 01.15.18

The Rockefeller University and Broad Institute of MIT and Harvard announce update to CRISPR-Cas9 portfolio filed by Broad

An update regarding inventorship and ownership of certain Broad filings relating to the use of the CRISPR-Cas9 system in eukaryotic cells

New York, NY, and Cambridge, Mass., January 15th, 2018

— The Rockefeller University and the Broad Institute of MIT and Harvard have settled their disagreement regarding inventorship and ownership of certain Broad filings relating to the use of the CRISPR-Cas9 system in eukaryotic cells. Rockefeller believed that its faculty member Dr. Luciano Marraffini, co-author with Broad’s Dr. Feng Zhang, on a seminal paper published in Science in 2013, Multiplex Genome Engineering Using CRISPR/Cas Systems, should have been maintained in these Broad eukaryote filings.

SOURCE

https://www.broadinstitute.org/news/rockefeller-university-and-broad-institute-mit-and-harvard-announce-update-crispr-cas9

 

That Other CRISPR Patent Dispute

It’s possible the Rockefeller dispute may work its way in to the interference proceedings involving the Broad and UC Berkeley. Earlier this summer, the patent examiner on the Rockefeller’s application gave an initial rejection to some of the claims because they overlap with UC Berkeley’s patent application. Sherkow said it’s possible the examiner’s decision could be used as evidence to persuade the patent judges that Berkeley was first to develop CRISPR as a gene-editing tool.

SEE

Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decisionruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

https://pharmaceuticalintelligence.com/2017/04/13/gene-editing-consortium-of-biotech-companies-crispr-therapeutics-crsp-intellia-therapeutics-ntla-caribou-biosciences-and-ers-genomics-uc-berkeley-doudnas-ip-and-university-of-vienna-charpe/

Other potential casualties of the Rockefeller dispute are some of the Broad’s patents overseas, as Catherine Coombs describes today (August 31) in an opinion article. In a nutshell, patents abroad may be compromised if the applicants on US patents are not the same as those listed on corresponding international patents, Coombs explains.

Rockefeller, Marraffini, and Zhang all declined to comment on the ongoing dispute. The Broad offered a statement acknowledging that Rockefeller has been an important collaborator on CRISPR, and that the institutions share a couple of patent applications related to the tool’s application in prokaryotic cells. “Rockefeller has raised the question of whether its interests are more general,” the statement reads. “We appreciate that Rockefeller has raised this question and expect it will be resolved amicably between our institutions. This resolution will likely take some time.”

The disagreement between Rockefeller and the Broad concerns just one of hundreds of CRISPR-related patent families, noted Corinne Le Buhan, the CEO of IPStudies, a Switzerland-based firm that tracks CRISPR patents. Le Buhan said it’s likely more patent fights will arise. “There are lots of very close patents signed by different inventors,” she told The Scientist. “Based on what we’ve seen on the technology side we can anticipate there will be more disputes.”

SOURCE

https://www.the-scientist.com/?articles.view/articleNo/46921/title/That-Other-CRISPR-Patent-Dispute/

CLASHES OVER THE FUTURE OF GENE THERAPY AT THE US’ BIGGEST BIOTECH MEETING, JP Morgan, SF, January 9-12, 2018

Role of Immune system in gene therapy using CRISPR Cas9

https://www.wired.com/story/clashes-over-the-future-of-gene-therapy-at-the-uss-biggest-biotech-meeting/

 

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CRISPR Based Research Awarded NHGRI Grants, The University of California, Berkeley’s Doudna will receive $2.1 million and The Broad Institute’s Zhang will receive $1.1 million

Reporter: Aviva Lev-Ari, PhD, RN

2.1.5.4

2.1.5.4   CRISPR Based Research Awarded NHGRI Grants, The University of California, Berkeley’s Doudna will receive $2.1 million and The Broad Institute’s Zhang will receive $1.1 million, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 10/10/2017

Gene Editing Market: CRISPR/CAS9 to be the fastest-growing technology segment – 2024

Request for Sample Copy of this Report @ http://bit.ly/2wExTM9

Rising prevalence of cancer, infectious diseases, and other genetic disorders, and growing demand for personalized medicine should stimulate industry expansion. Furthermore, expansion and development in healthcare infrastructure should propel industry demand.

Gene editing market has its extensive application in therapeutic areas of hematology, infectious disease, oncology and muscular diseases. Hematology was recognized as the highest revenue generating segment in 2015, due to extensive use in investigating genetic function in experimental hematology. Infectious disease segment will also follow the robust growth trend with 15.2% CAGR during the forecast timeframe contributing to the overall revenue of over USD 2.5 billion by 2024.

For more information visit @ http://bit.ly/2firtKv

Growth Drivers:

1. Increased funding for genetics research
2. Increased R&D expenditure and growth of biotechnology
3. Increasing demand for synthetic genes
4. Growing use of genetically modified technology
5. Technology advancements

SOURCE

https://www.linkedin.com/groups/1907871/1907871-6322402100114489346?midToken=AQGWu2im3_6Knw&trk=eml-b2_anet_digest_of_digests-hero-11-discussion~subject&trkEmail=eml-b2_anet_digest_of_digests-hero-11-discussion~subject-null-7gtb2~j8lx06xl~ig-nullcommunities~group~discussion&lipi=urn%3Ali%3Apage%3Aemail_b2_anet_digest_of_digests%3BLXMNlwc3Q32rTtwL%2FO%2BYbg%3D%3D

Jennifer Doudna of University of California, Berkeley, and Feng Zhang of the Broad Institute have both received separate grants from the National Human Genome Research Institute (NHGRI) for projects based on CRISPR technology.

Jennifer Doudna will receive $2.1 million to set up and run the Centre for Genome editing and Recording. The centre will address the challenges of accurately interrogating and manipulating DNA sequences in situ “at a scale and level of accuracy and not currently available” by developing technologies based on CRISPR-Cas9 that can “detect, alter and record the sequence and output of the genome in individual cells and tissues,” according to Doudna’s grant proposal.

Feng Zang will receive $1.1 million for a project that aims to develop a suite of tools for the interrogation of RNA based on CRISPR-Cas enzymes that target RNA in a programmable manner.

“Tools for transcript knockdown, translation upregulation, and transcript sensing will be developed, which, together, will enable dissection of genetic circuits in a dynamic, high-throughput manner, accelerating nearly all areas of biomedical science,” Zhang’s grant proposal said.

Doudna and Zhang both say they have the potential to advance the tool’s usefulness for human health purposes.

http://www.frontlinegenomics.com/news/14261/crispr-based-research-awarded-nhgri-grants/

https://www.genomeweb.com/research-funding/jennifer-doudna-feng-zhang-awarded-nhgri-grants-crispr-based-research

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Appellate Brief Seeking Reversal of U.S. Patent Board Decision on CRISPR/Cas9 Gene Editing, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Appellate Brief Seeking Reversal of U.S. Patent Board Decision on CRISPR/Cas9 Gene Editing

Reporter: Aviva Lev-Ari, PhD, RN

[Boldface added]

  • Appeal seeks reversal of Patent Trial and Appeal Board decision terminating interference without determining priority of inventorship of CRISPR/Cas9 gene editing
  • Brief asserts that the Board failed to properly apply controlling U.S. Supreme Court and Federal Circuit precedents, and ignored evidence of multiple groups readily applying CRISPR/Cas9 gene editing to eukaryotic cells following teachings of Charpentier-Doudna team

As explained in UC’s brief, application of the correct legal standards to the case is believed to require reversal of the PTAB’s decision. For these reasons, UC requests that the Federal Circuit instruct the PTAB to reinstate the interference proceeding so that it can properly determine priority of inventorship, as previously requested by UC. The PTAB’s failures to consider pertinent evidence and apply appropriate legal standards should at the very least require the matter to be remanded so that the PTAB can properly consider the evidence related to obviousness and Broad’s no-interference-in-fact motion using appropriate legal standards.
In the PTAB’s February decision terminating the interference proceeding prematurely, it had not yet considered the teachings of UC’s own prior-filed patent application with respect to using CRISPR/Cas9 in eukaryotic cells. Instead, the PTAB only addressed the threshold question of whether use in eukaryotic cells can be separately patentable from use in all settings as covered by UC’s claims. However, determinations on the underlying substantive matters have recently been made in parallel prosecution before the U.S. Patent & Trademark Office (“USPTO”). The USPTO has rejected a series of patent applications filed by Broad that are directed to uses of CRISPR/Cas9 technology in eukaryotic cells as being non-novel in view of UC’s prior-filed patent application, which the USPTO examiners considered to have effectively taught use of the CRISPR/Cas9 technology in eukaryotic cells. In addition, patent applications filed by Sigma-Aldrich and Toolgen that similarly claim use of CRISPR/Cas9 in eukaryotic cells (both of which filed applications before Broad’s application) have likewise recently been rejected as being either non-novel or obvious in view of the prior-filed UC patent application with specific respect to its teachings regarding application of the invention to use in eukaryotic cells.

SOURCES

On 7/25/2017

CRISPR Therapeutics, Intellia Therapeutics, Caribou Biosciences and ERS Genomics Announce Appellate Brief Seeking Reversal of U.S. Patent Board Decision on CRISPR/Cas9 Gene Editing

https://globenewswire.com/news-release/2017/07/25/1058142/0/en/CRISPR-Therapeutics-Intellia-Therapeutics-Caribou-Biosciences-and-ERS-Genomics-Announce-Appellate-Brief-Seeking-Reversal-of-U-S-Patent-Board-Decision-on-CRISPR-Cas9-Gene-Editing.html

On 4/13/2017:

Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decisionruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/04/13/gene-editing-consortium-of-biotech-companies-crispr-therapeutics-crsp-intellia-therapeutics-ntla-caribou-biosciences-and-ers-genomics-uc-berkeley-doudnas-ip-and-university-of-vienna-charpe/

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Innovations on the CRISPR System for Gene Editing: (1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage (2) New tool testing an entire genome against a CRISPR molecule to predict potential errors and interactions, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Innovations on the CRISPR System for Gene Editing: (1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage (2) New tool testing an entire genome against a CRISPR molecule to predict potential errors and interactions

Curator and Reporter: Aviva Lev-Ari, PhD, RN

 

Boom in human gene editing as 20 CRISPR trials gear up

A pioneering CRISPR trial in China will be the first to try editing the genomes of cells inside the body, in an effort to eliminate cancer-causing HPV virus

https://www.newscientist.com/article/2133095-boom-in-human-gene-editing-as-20-crispr-trials-gear-up/

 

(1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage

Harvard Medical School and Cornell University scientists have now generated near-atomic resolution snapshots of CRISPR that reveal key steps in its mechanism of action. The findings, published in Cell on June 29, provide the structural data necessary for efforts to improve the efficiency and accuracy of CRISPR for biomedical applications.

Through cryo-electron microscopy, the researchers describe for the first time the exact chain of events as the CRISPR complex loads target DNA and prepares it for cutting by the Cas3 enzyme. These structures reveal a process with multiple layers of error detection—a molecular redundancy that prevents unintended genomic damage, the researchers say.

 

Image Source: CRISPR forms a “seed bubble” state, which acts as an initial fail-safe mechanism to ensure that CRISPR RNA matches its target DNA. Image: Liao Lab/HMS

 

In contrast to the scalpel-like Cas9, CRISPR-Cas3 acts like a shredder that chews DNA up beyond repair. While CRISPR-Cas3 has, thus far, limited utility for precision gene editing, it is being developed as a tool to combat antibiotic-resistant strains of bacteria. A better understanding of its mechanisms may broaden the range of potential applications for CRISPR-Cas3.

In addition, all CRISPR-Cas subtypes utilize some version of an R-loop formation to detect and prepare target DNA for cleavage. The improved structural understanding of this process can now enable researchers to work toward modifying multiple types of CRISPR-Cas systems to improve their accuracy and reduce the chance of off-target effects in biomedical applications.

SOURCE

Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System

Yibei Xiao3

,

Min Luo3

,

Robert P. Hayes4

,

Jonathan Kim

,

Sherwin Ng

,

Fang Ding

,

Maofu Liao'Correspondence information about the author Maofu Liao

,

Ailong Ke5,'Correspondence information about the author Ailong Ke
3These authors contributed equally
4Present address: Merck & Co., 770 Sumneytown Pike, West Point, PA 19486, USA
5Lead contact
Bringing CRISPR into Focus – New study reveals key steps in CRISPR-Cas3 function at near-atomic resolution
By KEVIN JIANG
June 29, 2017
Scientists from The University of Texas at Austin may have come up with a possible solution. They’ve developed something that works like a predictive editor for CRISPR: a method for anticipating and catching the tool’s mistakes as it works, thereby allowing for the editing of disease-causing errors out of genomes.
Many forms of cancer, Huntington’s disease, and even HIV can be targeted using CRISPR. CRISPR can “correct” something that was actually right — the consequences of which can make it a dangerous mistake. One that actually causes a disease. CRISPR molecules—proteins that find and edit genes—sometimes target the wrong genes, acting more like an auto-correct feature that turns correctly spelled words into typos. Editing the wrong gene could create new problems, such as causing healthy cells to become cancerous.

“You and I differ in about 1 million spots in our genetic code,” says Ilya Finkelstein, an assistant professor in the Department of Molecular Biosciences at UT Austin and the project’s principal investigator. “Because of this genetic diversity, human gene editing will always be a custom-tailored therapy.”

Image Source: The heart of the new technique developed by Finkelstein, et al. for detecting interactions between CRISPR and off-target DNA segments is a standard next generation gene sequencing slide (a.k.a. flowcell), produced by Illumina. Image by Wikimedia user Bainscou, via Creative Commons Attribution 3.0 license
CHAMP, or Chip Hybridized Affinity Mapping Platform. The heart of the test is a standard next generation genome sequencing chip already widely used in research and medicine. Two other key elements—designs for a 3-D printed mount that holds the chip under a microscope and software the team developed for analyzing the results—are open source. As a result, other researchers can easily replicate the technique in experiments involving CRISPR.

Andy Ellington, a professor in the Department of Molecular Biosciences and vice president for research of the Applied Research Laboratories at UT Austin, is a co-author of the paper. He says this method also illustrates the unpredictable side benefits of new technologies.

“Next generation genome sequencing was invented to read genomes, but here we’ve turned the technology on its head to allow us to characterize how CRISPR interacts with genomes,” says Ellington. “Inventive folks like Ilya take new technologies and extend them into new realms.”

they found that the CRISPR molecule they tested, called Cascade, pays less attention to every third letter in a DNA sequence than to the others.

Discussion

CHAMP repurposes sequenced and discarded chips from modern next-generation Illumina sequencers for high-throughput association profiling of proteins to nucleic acids. A key difference between CHAMP and prior NGS-based approaches is that it does not require any hardware or software modifications to discontinued Illumina sequencers (Nutiu et al., 2011Tome et al., 2014Buenrostro et al., 2014). In CHAMP, all association-profiling experiments are carried out on sequenced MiSeq chips and imaged in a conventional TIRF microscope. CHAMP’s computational strategy uses phiX clusters as alignment markers to align the spatial information obtained via Illumina sequencing with the fluorescent association profiling experiments. This strategy offers three key advantages over previous approaches. First, using a conventional fluorescence microscope opens new experimental configurations, including multi-color co-localization and time-dependent kinetic experiments. The excitation and emission optics can also be readily adapted for FRET (Figure S6) and other advanced imaging modalities. Second, complete fluidic access to the chip allows addition of other protein components during a biochemical reaction. Third, the computational strategy for aligning sequencer outputs to fluorescent datasets is applicable to all modern Illumina sequencers, including the MiSeq, NextSeq, and HiSeq platforms. Indeed, we also used the CHAMP imaging and bioinformatics pipeline to regenerate, image, and spatially align the DNA clusters in a HiSeq flowcell (Figure S6), providing an avenue for massively parallel profiling of protein-nucleic acid interactions on both synthetic libraries and entire genomes. Future extensions will leverage on-chip transcription and translation (e.g., ribosome display) to facilitate high-throughput studies of RNA or peptide association landscapes. These studies will permit quantitative biophysical studies of diverse protein-nucleic acid interactions.

http://www.cell.com/cell/fulltext/S0092-8674(17)30637-2

SOURCE

Massively Parallel Biophysical Analysis of CRISPR-Cas Complexes on Next Generation Sequencing Chips

Cheulhee Jung8

,

John A. Hawkins8

,

Stephen K. Jones Jr.8

,

Yibei Xiao

,

James R. Rybarski

,

Kaylee E. Dillard

,

Jeffrey Hussmann

,

Fatema A. Saifuddin

,

Cagri A. Savran

,

Andrew D. Ellington

,

Ailong Ke

,

William H. Press

,

Ilya J. Finkelstein9,'Correspondence information about the author Ilya J. Finkelstein
8These authors contributed equally
9Lead Contact

This New Gene-Editing Technique Can Spot CRISPR’s Mistakes

New Technique Enables Safer Gene-Editing Therapy Using CRISPR

Other related articles on CRISPR published on this Open Access Online Scientific Journal include the following:

255 Articles on CRISPR

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GENE EDITING: Promises and Challenges: HSPH and NBC News Digital, Friday, May 19, 2017  Live webcast: 12:30-1:30pm ET

Reporter: Aviva Lev-Ari, PhD, RN

2.1.4.4

2.1.4.4   GENE EDITING: Promises and Challenges: HSPH and NBC News Digital, Friday, May 19, 2017  Live webcast: 12:30-1:30pm ET, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

THE ANDELOT SERIES

ON CURRENT SCIENCE CONTROVERSIES

GENE EDITING: Promises and Challenges 

Presented jointly with NBC News Digital

Friday, May 19, 2017

Live webcast: 12:30-1:30pm ET

ForumHSPH.org

In labs and in clinical trials, scientists are seeking ways to rewrite DNA, a building block of life. Tools such as zinc-finger nucleases (ZFNs), TAL effector nucleases (TALENs) and, more recently, CRISPR/Cas9 have the power to seek out and replace faulty DNA. The possibilities seem almost limitless: with the ability to edit DNA at will, researchers theoretically could wipe out malaria-causing mosquitos, make disease- and pest-proof crops without the need for pesticides, and cure genetic diseases, such as sickle cell anemia and cystic fibrosis. Cancer is another target, with human clinical trials using CRISPR already underway, while, in separate efforts, HIV has been reportedly eliminated in mice thanks to the tool.

But scientists and ethicists alike are worried about the speed at which the gene editing field is moving — and the implications of the results. In this panel, we will discuss the promises and challenges presented by gene editing for individual and public health. What scientific and ethical hurdles must be overcome before tools like CRISPR and others can move safely and more widely out of the lab and into fields, farms, and hospitals? 

EXPERT PARTICIPANTS

 

George Annas, Distinguished Professor at Boston University and Director of the Center for Health Law, Ethics & Human Rights at Boston University School of Public Health

 

Flaminia Catteruccia, Associate Professor of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health

 

George Church, Professor of Genetics, Harvard Medical School, and Co-Founder, Editas and eGenesis

MODERATOR

 

David Freeman, Editorial Director, NBC News MACH

Additional panelists may be announced.

Spread the word:

Send our panelists questions in advance to theforum@hsph.harvard.edu

We’ll be conducting a live chat on The Forum’s Gene Editing web page.

Tweet us @ForumHSPH  #GeneEditing

Forum video will be posted on-demand after the event.

SOURCE

From: “The Forum at Harvard T.H. Chan School of Public Health” <theforum=hsph.harvard.edu@mail168.atl171.mcdlv.net> on behalf of “The Forum at Harvard T.H. Chan School of Public Health” <theforum@hsph.harvard.edu>

Reply-To: “The Forum at Harvard T.H. Chan School of Public Health” <theforum@hsph.harvard.edu>

Date: Monday, May 15, 2017 at 2:36 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Gene Editing: Promises and Challenges

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Doudna and Charpentier and their teams to receive wide-ranging patents in many countries:  European Patent Office (EPO) and UK Intellectual Property Office – broad patent for CRISPR-Cas9 gene-editing technology to the University of California and the University of Vienna, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Doudna and Charpentierand their teams to receive wide-ranging patents in many countries:  European Patent Office (EPO) and UK Intellectual Property Office – broad patent for CRISPR-Cas9 gene-editing technology to the University of California and the University of Vienna

Reporter: Aviva Lev-Ari, PhD, RN

 

The EPO patent will cover the single-guide CRISPR-Cas9 technology in cells of all types. The technology was invented by Jennifer Doudna, a UC Berkeley professor of molecular and cell biology, Charpentier, now director of the Max Planck Institute for Infection Biology in Berlin, and their colleagues. Applications include treatment of various human diseases, as well as veterinary, agricultural and other biotech applications. The European patent would cover some 40 countries, including France, Germany, Italy, Spain, the Netherlands and Switzerland.

The EPO has stated its intent to grant a patent with claims that encompass all cells, despite objections from third parties, including the Broad Institute, a joint research institute of Harvard University and the Massachusetts Institute of Technology.

“We are excited that this patent will issue based on the foundational research we published with Emmanuelle Charpentier and the rest of our team. We look forward to the continued applications of gene-editing technology to solve problems in human health and agriculture,” said Doudna, who is a Howard Hughes Medical investigator at UC Berkeley.

The UC patent application to the EPO was substantially the same as the UC patent application filed in the United States. In the U.S., UC claims covering the use of single-guide CRISPR-Cas9 technology in any setting were found to be allowable by the U.S. Patent & Trademark Office, and were placed in an interference with patents owned by the Broad Institute that cover use of the technology in eukaryotic cells. An interference is a formal legal proceeding before the Patent Trial and Appeal Board (PTAB) to determine who was the first to invent.

“We disagree with the recent PTAB decision to terminate the interference between claims of the UC and the Broad Institute, and we are keeping all of our options open, including the possibility of an appeal,” Penhoet said. “We remain confident that when the inventorship question is finally answered, the Doudna and Charpentier teams will prevail.”

WATCH VIDEO

SOURCE

http://news.berkeley.edu/2017/03/28/european-patent-office-to-grant-uc-a-broad-patent-on-crispr-cas9/

Other related articles published in this Open Access Online Scientific Journal include the following:

Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decision ruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

https://pharmaceuticalintelligence.com/2017/04/13/gene-editing-consortium-of-biotech-companies-crispr-therapeutics-crsp-intellia-therapeutics-ntla-caribou-biosciences-and-ers-genomics-uc-berkeley-doudnas-ip-and-university-of-vienna-charpe/

 

Keyword Search: CRISPR – 247 articles in pharmaceuticalintelligence.com

https://pharmaceuticalintelligence.com/?s=CRISPR

 

Read Full Post »

UPDATED – Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decision ruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED – Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decision ruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

 

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 8/1/2019

Unpatentable claims

In its newest brief, UC identified a list of motions it would like permission to file with the PTAB. Among these motions, UC has asked the PTAB to judge all the Broad’s claims involved in the interference unpatentable.

First, UC alleges that the Broad’s patents fall under the provisions of AIA’s “first to file” system. All of the Broad’s involved cases issued from applications with a filing date on or after March 16, 2013 when the AIA took effect, but claim priority benefit to one or more applications filed before that date, the motion said. However, the Broad’s involved cases and/or the applications involved in the cases “contains or contained at one time at least one claim that was not supported by Broad’s applications filed before March 16, 2013,” the university added. “Thus, Broad’s involved cases, the application from which each of Broad’s involved patents issued, and/or a parent application to which each of Broad’s involved cases claims benefit, contains or contained at one time at least one claim to subject matter having an effective filing date on or after March 16, 2013 — thereby subjecting each of Broad’s involved cases to AIA prior art provisions.”

In its filing, UC noted that this motion should be enough for the PTAB to decide the unpatentability of the Broad’s claims. However, the filing adds, if this argument isn’t enough, there are other provisions that would render the Broad’s claims unpatentable.

Misidentified inventors

In the next motion, UC claims that “Broad deliberately misidentified the inventors on its involved patents and application, as demonstrated by the fact that its own prosecuting attorney’s sworn declaration contradicts the inventive entities named during prosecution of the involved applications.”

The Broad’s patents name either Zhang as the sole inventor or Zhang in combination with Le Cong, Fei Ran, Randall Platt, Patrick Hsu, and/or Sanjana. However, UC claims, Broad attorney Thomas Kowalski identified “a substantially different set of inventors” in a declaration provided to the European Patent Office.” Specifically, Kowalski’s declaration attests that several individuals who weren’t listed on the official patents “had contributed in a not insubstantial manner” to various CRISPR inventions, including Cong, Ran, Shuailiang Lin, Platt, Ophir Shalem, Matthias Heidenreich, and Lukasz Swiech.

“As one example, Broad’s attorney determined that Dr. Cong contributed to the invention of ‘the CRISPR-Cas9 system adapted in for [sic] uses in eukaryotic cells,’ a critical feature of every involved claim in the Interference. But Dr. Cong is not named on 8 of the 14 patents/application involved,” UC’s motion notes. “If all inventors are not named, then a patent or application is unpatentable unless it is corrected.”

“Inequitable… untrue… materially false”

UC’s next motion, alleging the Broad engaged in “inequitable conduct” is the most explosive, however.

The university said that the Broad’s claims are unpatentable because it made “at least one affirmative material misstatement” in each of its applications. Specifically, UC alleges that Zhang made statements he knew to be “untrue” at the time he made them, and that Sanjana had made a “materially false declaration.”

Zhang alleged in his declaration that he had a complete conception and reduction to practice of the technology he’d claimed he’d invented, USC said. But the university alleges that the evidence shows Zhang’s experiments failed to include tracrRNA, which is a required component of a functional CRISPR-Cas9 cleavage complex.

“The evidence shows that Dr. Zhang did not include tracrRNA in his experiments to form a CRISPR-Cas9 complex at that time and therefore could not have had a complete conception, much less a reduction to practice, of a functional CRISPR-Cas9 system for cleaving DNA,” UC wrote.

The university also claimed that Zhang didn’t include tracrRNA in his CRISPR-Cas9 complex until after he’d read a 2012 Science paper co-authored by Doudna, Charpentier, and Martin Jinek, which showed that tracrRNA is essential for cleavage of target DNA.

“Dr. Zhang was aware of the Jinek paper, and cited it in his own publications before he signed his declaration and before his counsel submitted it to the [USPTO],” UC said.

UC also accused Zhang of omitting unfavorable data and context from a summary panel the Broad showed the patent office. The full data would have showed the experimental failure of not including tracrRNA, as well as Zhang’s “failure to understand the criticality of tracrRNA at the time he conducted the experiments,” UC said.

“The Broad’s affirmative mischaracterization of data… is part of a larger pattern of deception,” the university added. In filing a claim for one of the involved patents, the Broad submitted a declaration from Sanjana, stating that the researchers had achieved successful cleavage of target DNA in eukaryotic cells by a CRISPR-Cas9 system comprising a single-guide RNA. As evidence, the team included a copy of an experimental gel. But UC said that gel was misrepresented, and clearly shows that Zhang and Sanjana’s experiment was “a failure.”

By presenting the gel as proof of a successful experiment, UC added, “Sanjana materially misstated facts in an attempt to prove an even earlier date of invention. Those acts evidence Broad’s pattern of deceptive behavior in its dealings with the patent office.”

In its supporting documents, UC submitted a February 2015 email from Shuailiang Lin, a researcher who had worked in Zhang’s lab from 2011 to 2012 and who was listed as an inventor on the Broad’s provisional applications.

“The 15-page declaration of [Feng Zhang] and Le Cong’s luciferase data is mis- and overstated to change the examiner’s decision, which seems to be a joke. After seeing your in virto [sic, in vitro] paper, Feng Zhang and Le Cong quickly jumped to the project without letting me know. My lab notebooks, emails and other files like dropbox or gel pictures recorded every step of the lab’s failure process. I am willing to give more details and records if you are interested or whoever is interested to clear the truth. We did not work it out before seeing your paper, it’s really a pity,” the e-mail said, according to UC’s filing.

The bottom line, UC concluded, is that the Broad’s patents should be canceled.

SOURCE

https://www.genomeweb.com/business-news/crispr-patent-fight-turns-ugly-uc-accuses-broad-researchers-lying-about-claims#.XUNJBJNKggo

https://www.statnews.com/2019/07/31/latest-crispr-patent-fight-mudslinging/

https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106115&identifier2=null&tabSel=4&action=filecontent&replyTo=PublicView.jsp

 

UPDATED on 3/2/2019

U.S. patent office indicates it will issue third CRISPR patent to UC

Patent involved in interference proceedings will add to university’s gene-editing portfolio

The U.S. Patent and Trademark Office has issued a notice of allowance for a University of California patent application covering systems and methods for using single molecule guide RNAs that, when combined with the Cas9 protein, create more efficient and effective ways for scientists to target and edit genes. U.S. patent application number 13/842,859, which had notably been examined in advance of a prior interference proceeding involving the Broad Institute, specifically focuses on methods and systems for modifying a target DNA molecule in any setting, both in vitro and within live cells, using one or multiple single guide RNAs, across every cell type. The associated patent is expected to issue in the next 6-9 weeks.

This CRISPR-Cas9 DNA-targeting technology, invented by Jennifer Doudna and Martin Jinek of the University of California, Berkeley, along with Emmanuelle Charpentier at Umea University and Krzystof Chylinski at the University of Vienna, is a fundamental molecular tool for editing genes. Together, this patent application and prior U.S. Patent Numbers 10,000,772 and 10,113,167, cover CRISPR-Cas9 methods and compositions useful as gene-editing scissors in any setting, including in vitro, as well as within live plant, animal and human cells.

“We are pleased the patent application is now allowed and that the issued patent will encompass the use of CRISPR-Cas9 technology in any cellular or non-cellular environment. We expect to see continued momentum in the expansion of UC’s CRISPR patent portfolio in the coming months,” said Eldora L. Ellison, Ph.D., lead patent strategist on CRISPR matters for the University of California and a director at Sterne, Kessler, Goldstein & Fox. “The steadfast protection of the CRISPR intellectual property pioneered by the Doudna-Charpentier team is wholly focused on the improvement of human welfare.”

SOURCE

https://news.berkeley.edu/2019/02/08/u-s-patent-office-indicates-it-will-issue-third-crispr-patent-to-uc/

UPDATED on 11/22/2017

John Leonard to helm Intellia

SOURCE

https://endpts.com/synergy-ceo-passes-torch-to-cco-troy-hamilton-president-steven-kafka-resigns-from-foundation-abbvie-vet-john-leonard-to-helm-intellia/?utm_medium=email&utm_campaign=376%20Friday%20122217%20Year-end%20biotech%20bash%20FDA%20approves%20record%2046th%20drug%20Roche%20triggers%2017B%20buyout%20JJ%20pays%20350M%20for%20BCMA%20pact&utm_content=376%20Friday%20122217%20Year-end%20biotech%20bash%20FDA%20approves%20record%2046th%20drug%20Roche%20triggers%2017B%20buyout%20JJ%20pays%20350M%20for%20BCMA%20pact+CID_1bdfc3dd8fa117ef7d943125e8d312d8&utm_source=ENDPOINTS%20emails&utm_term=Synergy%20CEO%20passes%20torch%20to%20CCO%20Troy%20Hamilton%20President%20Steven%20Kafka%20resigns%20from%20Foundation%20AbbVie%20vet%20John%20Leonard%20to%20helm%20Intellia

See Background:

UPDATED – Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century

 

|
Source: Intellia Therapeutics, Inc.
  • Appeal to the U.S. Court of Appeals for the Federal Circuit seeks review and reversal of the Patent Trial and Appeals Board’s (PTAB) decision to terminate CRISPR/Cas9 interference
  • In parallel, the companies and their licensors plan to pursue additional patents in the U.S. and worldwide covering the CRISPR/Cas9 technology and its use in cellular and non-cellular settings, including eukaryotic cells

BASEL, Switzerland;

CAMBRIDGE, Massachusetts;

BERKELEY, California;

DUBLIN, Ireland,

April 13, 2017

(GLOBE NEWSWIRE) — CRISPR Therapeutics (NASDAQ:CRSP), Intellia Therapeutics (NASDAQ:NTLA), Caribou Biosciences and ERS Genomics announced today that The Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively “UC”), co-owners of foundational intellectual property relating to CRISPR/Cas9 genome engineering, have appealed to the U.S. Court of Appeals for the Federal Circuit (the “Federal Circuit”) the decision by the Patent Trial and Appeal Board (“PTAB”) to terminate the interference between certain CRISPR/Cas9 patent claims owned by UC and patents and patent applications owned by the Broad Institute, Harvard University and the Massachusetts Institute of Technology (collectively, “Broad”).

In the appeal, UC is seeking review and reversal of the PTAB’s February 15, 2017 decision, which terminated the interference without determining which inventors actually invented the use of the CRISPR/Cas9 genome editing technology in eukaryotic cells. In its decision, the PTAB concluded that, although the claims overlap, the respective scope of UC and Broad’s claim sets as presented did not define the same patentable invention and, accordingly, terminated the interference without deciding which party first invented the use of the CRISPR/Cas9 technology in eukaryotic cells. UC is asking the Federal Circuit to review and reverse the PTAB’s decision.

In parallel with the appeal, UC is pursuing applications in the U.S. and other jurisdictions worldwide to obtain patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted in the United Kingdom, and the European Patent Office is also granting a patent to UC, which will issue on May 10, 2017. UC’s earliest patent application describing the CRISPR/Cas9 genome editing technology and its use was filed on May 25, 2012, while the Broad’s earliest patent application was filed more than six months later, on December 12, 2012.

The law firm of Munger, Tolles & Olson LLP will be handling the appeal, with Don Verrilli, former Solicitor General of the United States, as lead counsel.

SOURCE

https://globenewswire.com/news-release/2017/04/13/960152/0/en/CRISPR-Therapeutics-Intellia-Therapeutics-Caribou-Biosciences-and-ERS-Genomics-Announce-Appeal-of-CRISPR-Cas9-U-S-Patent-Board-Decision.html

 

Editas’ rivals appeal a recent setback on patent fight, mapping a global war for CRISPR supremacy

They say they are “pursuing applications in the U.S. and other jurisdictions worldwide to obtain patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells. Corresponding patents have already been granted in the United Kingdom, and the European Patent Office is also granting a patent to UC, which will issue on May 10, 2017. UC’s earliest patent application describing the CRISPR/Cas9 genome editing technology and its use was filed on May 25, 2012, while the Broad’s earliest patent application was filed more than six months later, on December 12, 2012.”

The group said today it is also waging a global patent battle for CRISPR/Cas9 supremacy over Editas and its scientific founder, Feng Zhang, who patented the rival technology at The Broad.

SOURCE

https://endpts.com/editas-rivals-appeal-a-recent-setback-on-patent-fight-mapping-a-global-war-for-crispr-supremacy/?utm_medium=email&utm_campaign=201%20Thursday%2041317%20Biogen%20Roche%20forge%2011B%20in%20deals%20for%20Bristol%20drugs%20Busy%20week%20for%20the%20biotech%20jobs%20scene&utm_content=201%20Thursday%2041317%20Biogen%20Roche%20forge%2011B%20in%20deals%20for%20Bristol%20drugs%20Busy%20week%20for%20the%20biotech%20jobs%20scene+CID_1d65272f5e757d7ae0245395295e6e12&utm_source=ENDPOINTS%20emails&utm_term=Editas%20rivals%20appeal%20a%20recent%20setback%20on%20patent%20fight%20mapping%20a%20global%20war%20for%20CRISPR%20supremacy

 

REFERENCES

Other press releases by Intellia Therapeutics, Inc.

Read Full Post »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

2.1.5.5

2.1.5.5   Promising research for a male birth control pill, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Scientists think excessive population growth is a cause of scarcity and environmental degradation. A male pill could reduce the number of unintended pregnancies, which accounts for 40 percent of all pregnancies worldwide.

But, big drug companies long ago dropped out of the search for a male contraceptive pill which is able to chemically intercept millions of sperm before they reach a woman’s egg. Right now the chemical burden for contraception relies solely on the female. There’s not much activity in the male contraception field because an effective solution is available on the female side.

Presently, male contraception means a condom or a vasectomy. But researchers from Center for Drug Discovery at Baylor College of Medicine, USA are renewing the search for a better option—an easy-to-take pill that’s safe, fast-acting, and reversible.

The scientists began with lists of genes active in the testes for sperm production and motility and then created knockout mice that lack those genes. Using the gene-editing technology called CRISPR, in collaboration with Japanese scientists, they have so far made more than 75 of these “knockout” mice.

They allowed these mice to mate with normal (wild type) female mice, and if their female partners don’t get pregnant after three to six months, it means the gene might be a target for a contraceptive. Out of 2300 genes that are particularly active in the testes of mice, the researchers have identified 30 genes whose deletion makes the male infertile. Next the scientists are planning a novel screening approach to test whether any of about two billion chemicals can disable these genes in a test tube. Promising chemicals could then be fed to male mice to see if they cause infertility.

Female birth control pills use hormones to inhibit a woman’s ovaries from releasing eggs. But hormones have side effects like weight gain, mood changes, and headaches. A trial of one male contraceptive hormone was stopped early in 2011 after one participant committed suicide and others reported depression. Moreover, some drug candidates have made animals permanently sterile which is not the goal of the research. The challenge is to prevent sperm being made without permanently sterilizing the individual.

As a better way to test drugs, Scientists at University of Georgia, USA are investigating yet another high-tech approach. They are turning human skin cells into stem cells that look and act like the spermatogonial cells in the testes. Testing drugs on such cells might provide more accurate leads than tests on mice.

The male pill would also have to start working quickly, a lot sooner than the female pill, which takes about a week to function. Scientists from University of Dundee, U.K. admitted that there are lots of challenges. Because, a women’s ovary usually release one mature egg each month, while a man makes millions of sperm every day. So, the male pill has to be made 100 percent effective and act instantaneously.

References:

https://www.technologyreview.com/s/603676/the-search-for-a-perfect-male-birth-control-pill/

https://futurism.com/videos/the-perfect-male-birth-control-pill-is-coming-soon/?utm_source=Digest&utm_campaign=c42fc7b9b6-EMAIL_CAMPAIGN_2017_03_20&utm_medium=email&utm_term=0_03cd0a26cd-c42fc7b9b6-246845533

http://www.telegraph.co.uk/women/sex/the-male-pill-is-coming—and-its-going-to-change-everything/

http://www.mensfitness.com/women/sex-tips/male-birth-control-pill-making

http://health.howstuffworks.com/sexual-health/contraception/male-bc-pill.htm

http://europe.newsweek.com/male-contraception-side-effects-study-pill-injection-518237?rm=eu

http://edition.cnn.com/2016/01/07/health/male-birth-control-pill/index.html

http://www.nhs.uk/Conditions/contraception-guide/Pages/male-pill.aspx

Read Full Post »

CRISPR Patent Battle Determined on 2/15/2017 – USPTO issues a verdict in legal tussle over rights to genome-editing technology, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

CRISPR Patent Battle Determined on 2/15/2017 – USPTO issues a verdict in legal tussle over rights to genome-editing technology

Curator: Aviva Lev-Ari, PhD, RN

Broad Institute prevails in heated dispute over CRISPR patents

Sharon Begley sharon.begley@statnews.com
@sxbegle

In a one-sentence judgment by the Patent Trial and Appeal Board, the three judges decided that there is “no interference in fact.” In other words, key CRISPR patents awarded to the Broad beginning in 2014 are sufficiently different from patents applied for by UC that they can stand. The judges’ full 51-page decision explaining their reasoning stated that the Broad had persuaded them “that the parties claim patentably distinct subject matter.”

https://www.statnews.com/2017/02/15/crispr-patent-ruling/#decision

MIT

The Broad said in a statement that the decision “confirms that the patents and applications of Broad Institute and UC Berkeley are about different subjects and do not interfere with each other.”

UC, Berkeley

In a statement, the University of California said it was pleased that its patent application, which it described as covering “the invention and use of CRISPR gene editing in all cells,” can move forward. “We continue to maintain that the evidence overwhelmingly supports our position that the Doudna/Charpentier team was the first group to invent this technology for use in all settings and all cell types,” it said, “and that the Broad Institute’s patents directed toward use of the CRISPR-Cas9 system in particular cell types are not patentably distinct from the Doudna/Charpentier invention.”

UC said it is considering its legal options, including the possibility of an appeal, but it contended that anyone who wants to develop CRISPR-based treatments for human diseases would have to license not only the Broad’s patents but also those that UC expects to be awarded. “Ours,” Doudna told reporters, “is for the use [of CRISPR] in all cells,” including human ones.

PTAB appeals are heard by the US Court of Appeals for the Federal Circuit, which sits in Washington. In recent years, more than half of PTAB’s decisions have been upheld.

“The Federal Circuit heard three appeals of interferences in 2016,” said Sherkow. “All three were at least affirmed in part. It’s completely unclear whether that’s meaningful — it’s an N of 3–but there you go.” Overall, on 155 appeals since PTAB was created in 2012, the Federal Circuit affirmed 120 on every issue, dismissed or reversed 21 on every issue, and issued partial decisions (that is, upholding parts of a PTAB decision and reversing others) in the other 14.

https://www.statnews.com/2017/02/15/crispr-patent-ruling/#decision

Said UC attorney Lynn Pasahow:

For “all tennis balls,” read “all cells.” For “green tennis balls,” read “eukaryotic cells.”

https://www.statnews.com/2017/02/16/crispr-patent-decision-six-takeaways/

 

What will that mean for licensees of CRISPR patents?

Stanford University Voice

UC believes that any company that wants to use CRISPR to develop human therapies — we’re looking at you, Editas Medicine — will need to license not only the Broad’s patents on eukaryotic cells but also those UC expects to receive on all kinds of cells. “It looks to me as if someone wanting to use the Broad patent would also have to license the UC patent,” agreed law professor Hank Greely of Stanford University. “The UC patent (if granted) would be on any use; the Broad would be on use in eukaryotes. I think someone who wanted to do this in eukaryotes would need to have licenses to both.”

CRISPR-Cas9 is unlikely to be the last genome-editing technology ever discovered. In 2015, Zhang and his colleagues discovered a version called Cpf1, which they’ve now patented and licensed to Editas. “I continue to think the possibility of inventing around the [CRISPR] patents seems very likely,” said Stanford’s Greely. Bacteria “have certainly come up with other ways to reach the same end [of genome editing], ways that aren’t covered by UC’s or the Broad’s claims. That could make either of these patents ultimately of little importance … especially if the licensing conditions give people a strong incentive to come up with invent-arounds.” Science will march on.

https://www.statnews.com/2017/02/16/crispr-patent-decision-six-takeaways/

What does the CRISPR ruling mean for biotech?

By DAMIAN GARDE @damiangarde

FEBRUARY 15, 2017

Editas Medicine, which has aligned with the winning Broad, saw its share price rise more than 25 percent on Wednesday. Intellia Therapeutics, affiliated with UC, fell about 11 percent, while compatriot CRISPR Therapeutics dipped 24 percent.

https://www.statnews.com/2017/02/15/what-does-the-crispr-ruling-mean-for-biotech/

 

Broad Institute wins bitter battle over CRISPR patents

The US Patent and Trademark Office issues a verdict in legal tussle over rights to genome-editing technology.

15 February 2017 Updated:In December 2016, lawyers representing the University of California and the Broad Institute participated in oral arguments before a trio of patent-court judges. University of California attorney Lynn Pasahow said that the team had not yet decided whether it would appeal the verdict on 2/15/2017.

Lawyers representing the University of California filed for an ‘interference’ proceeding, in an effort to have the Broad’s patents thrown out. But on 15 February, patent judges determined that there was no interference, meaning that the Broad’s invention is distinct from that of the University of California, and the Broad patents will stand. The University of California’s patent application will now be referred back to an examiner, but legal challenges could continue.

molecular biologist Jennifer Doudna of the University of California in Berkeley, likened the situation to licensing permission to someone who wants to use green tennis balls. “They will have a patent on the green tennis balls,” she said, referring to the Broad patents. “We will have a patent on all tennis balls.” ”Doudna argued at the press conference that the patent battle had not hampered research, given the speed with which researchers had taken up the technique and companies had rushed to commercialize it.”

The University of California’s invention would cover the design of the RNA molecule that guides the key step in CRISPR–Cas9 gene editing, directing the Cas9 enzyme to a specific site in the genome. But getting that system to work in eukaryotes was an additional inventive step, Coombes says, a patent lawyer at intellectual-property specialists HGF in York, UK.

SOURCE

Nature doi:10.1038/nature.2017.21502

http://www.nature.com/news/broad-institute-wins-bitter-battle-over-crispr-patents-1.21502?WT.ec_id=NEWSDAILY-20170216%20

https://www.statnews.com/2017/02/15/crispr-patent-ruling/#decision

Related articles from nature.com

Other related articles published in this Open Acceaa Online Scientific Journal include the following:

UPDATED – Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century: UC, Berkeley and Broad Institute @MIT

Reporter: Aviva Lev-Ari, PhD, RN

 

Read Full Post »

Top 50 Women in CRISPR : Women in CRISPR, Legal Status of Inventions and Declaration of the Heroes in CRISPR

Curator: Aviva Lev-Ari, PhD, RN

2.1.5.6

2.1.5.6   Top 50 Women in CRISPR : Women in CRISPR, Legal Status of Inventions and Declaration of the Heroes in CRISPR, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Part 1: Top 50 Women in CRISPR : Women in CRISPR 

See List, below

SOURCE

Part 2: UPDATED – Status “Interference — Initial memorandum” – CRISPR/Cas9 – The Biotech Patent Fight of the Century: UC, Berkeley and Broad Institute @MIT

Reporter: Aviva Lev-Ari, PhD, RN

SOURCE

https://pharmaceuticalintelligence.com/2016/01/06/status-interference-initial-memorandum-crisprcas9-the-biotech-patent-fight-of-the-century/

Part 3: The Heroes of CRISPR

in CELL, December, 2015

Eric S. Lander1,2,3,*

1, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA

2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

3Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA

*Correspondence: lander@broadinstitute.org

Three years ago, scientists reported that CRISPR technology can enable precise and efficient genome editing in living eukaryotic cells. Since then, the method has taken the scientific community by storm, with thousands of labs using it for applications from biomedicine to agriculture. Yet, the preceding 20-year journey—the discovery of a strange microbial repeat sequence; its recognition as an adaptive immune system; its biological characterization; and its repurposing for genome engineering—remains little known. This Perspective aims to fill in this backstory—the history of ideas and the stories of pioneers—and draw lessons about the remarkable ecosystem underlying scientific discovery.

SOURCE

http://dx.doi.org/10.1016/j.cell.2015.12.041

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Top 50 Women in CRISPR : Women in CRISPR

SOURCE
A B C D E F G H I J
1
Women in CRISPR/Cas9 genome editing research – List Version 3
2
First Name
Last Name Organisation Location Country Position Website
Twitter Handle
Field of Research
Research Interest
3
Divaki Bhaya Stanford Univeristy Stanford, CA USA Professor https://dpb.carnegiescience.edu/labs/bhaya-lab
Evolution and Ecology – microbial diversity – Plant Biology
Research in my lab is driven by an interest in understanding how photosynthetic microorganisms perceive and evolve in response to environmental stressors, such as light, nutrients and viral attack.We work both with model organisms and with cyanobacteria in naturally occurring communities. Recently,we have started to develop synthetic biology-inspired approaches to use in cyanobacteria.
4
Jill Banfield University of California Berkeley Berkeley, CA USA Professor http://nanogeoscience.berkeley.edu Evolution and Ecology – microbial diversity
The study system for this project is an aquifer adjacent to the Colorado River in Rifle, Colorado, USA.Research addresses knowledge gaps related to the roles of subsurface microbial communities in biogeochemical cycling. Given the link between the carbon cycle and global climate change, a particular interest in this work is the impact of microorganisms on carbon compounds buried in the terrestrial subsurface, both through respiration and carbon fixation.
5
Denis Bauer
Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Sydney Australia Head of laboratory http://people.csiro.au/B/D/Denis-Bauer.aspx @allPowerde Computational biology – Technology development
Dr. Denis Bauer is the team leader of the transformational bioinformatics team in CSIRO’s ehealth program. Her expertise is in high throughput genomic data analysis, computational genome engineering, as well as Spark/Hadoop and high-performance compute system.
6
Pilar Blancafort Harry Perkins Institute for Medical Research Perth Australia Associate Professor Cancer biology – Technology Development
The Blancafort laboratory focuses on the development of novel approaches to target cancers that are currently refractory to treatment and associated to poor outcome, such as triple negative breast cancers and ovarian cancers. At present, there are no targeted approaches to combat these tumors with chemotherapy and radiation the only treatment options. The laboratory generates novel functionalised molecules able to specifically target these tumors with minimal toxicity to normal cells. Our emphasis is in advanced stage metastatic tumors, which quasi invariably develop resistance. Ultimately we wish to revert the behavior of metastatic cells by sensitizing these treatment resistant tumors to chemotherapy regimes.
7
Alexa Burger University of Zurich Zurich Switzerland
Senior postdoctoral fellow
http://www.imls.uzh.ch/en/research/mosimann/labmembers.html @aburger2009 Zebrafish – Technology development
CRISPR application in Zebrafish (ribonucleic complex and increase mutation efficiency)
8
Emmanuelle Charpentier Max Plank Institute Berlin Germany Professor http://www.mpiib-berlin.mpg.de/research/regulation_in_infection_biology Host-pathogens interaction
Our research relates to the field of Molecular Infection Biology. We are overall interested in understanding the molecular mechanisms governing physiology-, virulence- and infection-associated processes in Gram-positive bacterial pathogens. We use a combination of genetic, genomic, molecular, biochemical, physiological and cell infection approaches to study mechanisms of gene expression at the transcriptional and post-transcriptional level in horizontal gene transfer, adaptation to stress, physiology or virulence. In particular, we do research on CRISPR, the adaptive immune system that protects bacteria against invading genetic elements; the small regulatory RNAs that interfere with bacterial pathogenicity; protein quality-control that regulates bacterial adaptation, physiology and virulence; and the mechanisms of bacterial recognition by immune cells.
9
Sylvia Comporesi Kings College London London UK Lecturer https://silviacamporesiresearch.org/about/ @silviacomporesi Bioethics
I am a bioethicist with an interdisciplinary background in medical biotechnologies, ethics and philosophy. I am a tenured Lecturer (the UK equivalent to Assistant Professor) in Bioethics & Society in the Department of Global Health & Social Medicine (formerly, Social Science, Health & Medicine) at King’s College London, where I direct the Master’s in Bioethics & Society.
10
Elena Conti Max Plank Institute Martinsried Germany
Group leader and Director
http://www.biochem.mpg.de/4877968/Research Structural Biology – RNA biology
Our group has a long-standing interest in RNA metabolism, with a particular focus on the molecular mechanisms of eukaryotic RNA transport and degradation.
11
Jennifer Doudna University of California Berkeley Berkeley, CA USA Professor http://rna.berkeley.edu/index.html @doudna_lab RNA biology – Adaptive immunity
Exploring molecular mechanisms of RNA-mediated gene regulation
12
Caixia Gao Chinese Academy of Science Beijing China Professor http://enpcce.genetics.cas.cn/PN/CXG/ACXG/ Plant biology (Wheat) – Technology development
The main research goal of our laboratory is to develop high-throughput transgene technologies for common wheat (Triticumaestivum L.) and maize (Zea mays) and other major crops to satisfy the needs of crop improvement and gene discovery.
13
Carine Giovanangeli Museum National d’Histoire Naturelle Paris France Director of Research http://biophysique.mnhn.fr/site/Modifications+génomiques+et+réponses+cellulaires DNA repair mechanisms – Technology development
Nowadays, we are mainly focusing on novel artificial DNA binding domains, the TALE repeats (transcription-activator like effector) and CRISPR/Cas9 system. We use the CRISPR/Cas or TALE as nucleases (TALEN) to study DNA repair in mammalian cells as well as DNA probes to study genome dynamics (see Repeated DNA sequences and chromatin).
14
Natalia Gomez-Ospina Stanford Univeristy Stanford, CA USA Clinical Instructor https://med.stanford.edu/profiles/natalia-gomez-ospina?tab=bio Stem cell biology – Clinical therapy
Dr. Gomez-Ospina was born and raised in Medellin, Colombia. She began her undergraduate studies in petroleum engineering at the Universidad Nacional de Colombia before moving to Colorado. She double majored at the University of Colorado Boulder, completing her bachelor’s degree in Molecular Cellular and Developmental Biology as well as Biochemistry. She graduated summa cum laude and wrote an honors thesis entitled “Role of the quiescent center in the regeneration of the root cap in Zea Mays.” She then completed her combined MD, PhD at Stanford Medical School, where her PhD work focused on understanding the novel functions of voltage-gated calcium channels. Her PhD thesis, “The calcium channel CACNA1C gene: multiple proteins, diverse functions,” was published in Cell. After completion of her dual degrees, she did her preliminary year in internal medicine at Santa Barbara Cottage hospital before starting residency in Dermatology at Johns Hopkins Hospital. She completed residency in Medical Genetics at Stanford Hospital and clinics. She is currently doing her post-doctoral research with Dr. Matthew Porteus in Pediatric Stem Cell transplantation, where she is developing a genome editing strategy in stem cells as a curative therapy for metabolic diseases. In addition to her research, Dr. Gomez-Ospina is a clinical instructor in Medical Genetics. For her clinical practice she sees patients with suspected genetic disorders, and is also in charge of the enzyme replacement service for lysosomal storage disorders at Lucile Packard Children’s hospital. She has been the lead author in research studies in The New England Journal of Medicine, Cell, Nature Communications, and American Journal of Medical Genetics.
15
Asma Hatoum-Aslan The University of Alabama Tuscaloosa, AL USA Assistant Professor http://bsc.ua.edu/asma-hatoum-aslan/ @crisprcas10 Host-pathogens interaction
Bacterial infectious diseases are a major cause of mortality worldwide. The rise in antibiotic resistant infections, coupled with the sharp decline in the discovery of new and clinically useful classes of antibiotics, underscores an urgent need for alternative strategies to combat bacterial infections. Small noncoding RNA pathways have recently been recognized as important regulators of bacterial pathogenesis, and the challenge lies in gaining a detailed understanding of these processes. My research uses the tools of biochemistry and molecular genetics to unravel the mechanisms of small RNA-mediated pathways and enable the development of novel anti-microbial therapeutics.
16
Rachel Haurwitz Caribou Biosciences Berkeley, CA USA
President and Chief Executive officer
http://cariboubio.com/about-us/management-team Biotech – Technology development
Rachel is a co-founder of Caribou Biosciences and has been President and CEO since its inception. She has a research background in CRISPR-Cas biology, and is also a co-founder of Intellia Therapeutics. In 2014, she was named by Forbes Magazine to the “30 Under 30” list in Science and Healthcare, and in 2016, Fortune Magazine named her to the “40 Under 40” list of the most influential young people in business. Rachel is an inventor on several patents and patent applications covering multiple CRISPR-derived technologies, and she has co-authored scientific papers in high impact journals characterizing CRISPR-Cas systems. Rachel earned an A.B. in Biological Sciences from Harvard College, and received a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley.
17
Sara Howden Murdoch Children Research Institute Melbourne Australia Senior Research Fellow Stem cell biology – Technology development
Around 10-20% of kidney disease is inherited. In children with kidney disease, this is closer to 50% although in many instances, the disease-causing mutation is unknown, therefore limiting treatment options. In our research group, we investigate the genes required for normal kidney development and what happens as a result of genetic or environmental damage during development. This knowledge is used to try to recreate kidney stem cells. We have developed methods for generating mini-kidneys from human stem cells that represent models of the human organ. We hope to use these mini-kidneys to screen drugs for kidney toxicity, as models with which to understand kidney disease, to generate cells for the treatment of kidney disease and eventually to bioengineer replacement organs.
18
Nina Hoyland-kroghsbo Princeton University Princeton, NJ USA Postdoctoral fellow http://molbiolabs.princeton.edu/bassler/members Host-pathogens interaction
Research Interest: The global threat of multi-drug resistant bacteria urgently demands alternatives to conventional antibiotics. Two promising alternatives to traditional antibiotics are bacteriophage (phage) therapy and inhibitors of bacterial cell-cell communication, known as quorum sensing (QS). Bacteria in high cell density maximally engage in QS. These cells are particularly vulnerable to phage infections, which could rapidly spread and kill the population. QS-control of antiphage activities would enable bacteria to specifically activate defenses when they are at the highest risk of infection. I am investigating to what extent bacteria use QS to regulate their antiphage defenses. Whereas QS-inhibitory compounds are generally studied for their capacity to inhibit bacterial virulence, I will study whether they additionally have the ability to increase the vulnerability of pathogenic bacteria to phages.
19
Danwei Huangfu Memorial Sloan Kettering New York, NY USA Head of laboratory https://www.mskcc.org/research-areas/labs/danwei-huangfu Stem cell biology – Technology development
The ability to program naïve cells or to reprogram differentiated cells into particular fates will open the door to the discovery of novel therapeutics for diseases such as diabetes. The goal of my lab is to understand the fundamental principles that govern the identity of a cell, and to use these principles to manipulate cell fates for regenerative medicine. In pursuit of this goal, we employ a variety of approaches including cellular programming and reprogramming through gene transduction, directed differentiation of embryonic stem (ES) cells, chemical screening, mouse genetics, adult tissue injury and regeneration, and tissue/cell transplantation.
20
Maria Jasin Memorial Sloan Kettering New York, NY USA Head of laboratory https://www.mskcc.org/research-areas/labs/maria-jasin DNA repair mechanisms – DSB
Human chromosomes are constantly assaulted by challenges to their integrity as a result of either environmental agents that damage DNA or from normal DNA metabolism. The failure to repair damaged DNA faithfully is ultimately responsible for many human diseases, especially cancer. This laboratory focuses on the repair of 1 particular lesion in DNA, the double-strand break (DSB). DSBs arise from agents, such as ionizing radiation, and can also occur spontaneously during DNA replication. Our emphasis is on repair of DSBs by homologous recombination, with a particular interest in the role of homologous recombination in maintaining genetic stability. Understanding the repair of DSBs is not only important for basic science and health concerns, but also impacts on molecular genetic manipulations of mammalian genomes
21
Josephin Johnston The Hasting Centre Garrison, NY USA Director of Research http://www.thehastingscenter.org/team/johnston/ @bioethicsjosie Bioethics
Josephine Johnston is an expert on the ethical, legal, and policy implications of biomedical technologies, particularly as used in human reproduction, psychiatry, genetics, and neuroscience.
22
Helene Jousset-Sabroux The Walter and Eliza Hall Institute for Medical Research Melbourne Australia Head of laboratory http://www.wehi.edu.au/people/hélène-jousset-sabroux
High Throughput Screening – Technology Development
The screening laboratory offers a wide range of expertise gained from both industrial and academic backgrounds, resulting in a professional ability to develop high capacity cellular or biochemical assays. We offer liquid handling robotics, plate readers and computing programs to increase the scale and speed of assays, and leverage automation to quickly assess the activity of a large number of compounds.
23
tamsin Lannagan University of Adelaide Adelaide Australia
Senior postdoctoral fellow
Cancer biology – Technology Development
My role within the group is to develop and assess novel mouse models of colorectal cancer, using colonoscopy techniques that are very similar to patient surveillance in humans. In addition, I am developing an in vitro method of growing mouse and human stem cells from the colon with their associated connective tissue. This will allow us to further investigate these support cells in normal growth and cancer. Both systems will be directly therapeutically relevant, allowing us to assess preclinical targeting of molecular pathways relevant to colorectal cancer.
24
Hong Li Florida State University Tallahassee, FL USA Professor http://biophysics.fsu.edu/hongli/ Structural Biology – RNA biology
A diverse range of RNA:protein, RNA:RNA and protein:protein interactions occur at the level of transcription and translation as well as post-transcriptional modifications. RNA:protein interactions are particularly interesting not only because they play important functional roles in assembly and biological processes, but also because the rules of their interactions are still poorly understood owing to the scarce structural data. Unlike DNA molecules, RNA can fold into a range of structures for interacting with proteins and small molecules. We hope, by providing exceptionally detailed images of the molecular events along the assembly and functional pathways, to unveil the underlying basis for assembly and functions involving RNA and partner proteins.
25
Jennifer Listgarten Microsoft Research Cambridge, MA USA Senior Researcher http://www.jennifer.listgarten.com Computational biology – Technology development
My area of expertise is in machine learning and applied statistics for computational biology. I’m interested in both methods development as well as application of methods to enable new insight into basic biology and medicine.
26
Shirley Liu Dana Farber Cancer Institute – Harvard Cambridge, MA USA Head of laboratory http://liulab.dfci.harvard.edu Computational biology – Technology development
We are developing the computational methods for the design (SSC), analysis (MAGeCK), hit prioritization (NEST), and visualization (VISPR) of genome-wide CRISPR screens. We are also using this technology to identify key genes in breast and prostate tumor progression and drug resistance. We also develop CRISPR screen platforms to understand the functions of enhancers and long-noncoding RNAs, and identify synthetic lethal gene pairs in cancer that leads to optimized cancer precision medicine.
27
Anita Marchfelder Ulm University Ulm Germany Head of laboratory https://www.uni-ulm.de/en/nawi/nawi-molbot/research/anita-marchfelder/ Host-pathogens interaction
All prokaryotic cells have to fend off foreign genetic elements like for instance viruses. To do that they have developed several different defence strategies. The recently discovered new defence strategy is the so called prokaryotic immune system also called CRISPR/Cas (CRISPR: clustered regularly interspaced short palindromic repeats, Cas: CRISPR-associated). It is adaptive, since cells can become immune against new invaders and it is heritable, since the information about the invader is stored in the genome. The CRISPR/Cas system consists of clusters of repetitive chromosomal DNA in which short palindromic DNA repeats are separated by spacers, the latter being sequences derived from the invader. In addition, a set of proteins, the Cas proteins, is involved in this defence reaction. We are investigating the CRISPR/Cas system in the halophilic archaeon Haloferax volcanii. Haloferax encodes a type I-B CRISPR/Cas system with eight Cas proteins and three CRISPR RNAs.
28
Karen Maxwell University of Toronto Toronto Canada Assistant Professor http://individual.utoronto.ca/maxwell_lab/ @theMaxwellLab Host-pathogens interaction
The Maxwell lab studies the phages that infect and kill the human bacterial pathogens Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Infections caused by these bacteria create a significant disease burden, and the increasing incidence of antibiotic resistant infections caused by these pathogens is one of our most serious health threats.
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Barbara J Meyer University of California Berkeley Berkeley, CA USA Head of laboratory http://mcb.berkeley.edu/labs/meyer/ Nematode – Technology development
Targeted Genome-editing Across Highly Diverged Nematode Species. Thwarted by the lack of reverse genetic approaches to enable cross-species comparisons of gene function, we established robust strategies for targeted genome editing across nematode species diverged by 300 MYR. In our initial work, a collaboration with Sangamo BioSciences, we used engineered nucleases containing fusions between the DNA cleavage domain of the enzyme FokI and a custom-designed DNA binding domain: either zinc-finger motifs for zinc-finger nucleases or transcription activator-like effector domains for TALE nucleases (TALENs). In those experiments, we allowed the DNA double-strand breaks to be repaired imprecisely by non-homologous end joining (NHEJ) to create mutations in precise locations.
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Shondra Miller Washington University St Louis, MO USA Director of Research http://geic.wustl.edu/technology/ Stem cell biology – Technology development
The Genome Engineering and IPSC Center (GEiC) was formed by the consolidation of two pre-existing cores, the Genome Engineering Center and the Induced Pluripotent Stem cell (iPSC) core, both established by the Department of Genetics in the past few years. These two Centers were established to facilitate functional genomic studies through the use of patient-derived iPSCs and the generation of modified cells and organisms using genome editing technologies.
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Hiromi Miura Tokai University School of Medicine Kanagawa Japan Assistant Professor https://www.researchgate.net/profile/Hiromi_Miura Mouse – Technology development
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Kathy Niakan The Francis Crick Institute London UK Head of laboratory https://www.crick.ac.uk/research/a-z-researchers/researchers-k-o/kathy-niakan/ Stem cell biology – Technology development
The allocation of cells to a specific lineage is regulated by the activities of key signalling pathways and developmentally regulated transcription factors. The focus of our research is to understand the influence of signalling and transcription factors on differentiation during early human development.
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Kate O’Connor-Giles University Wisconson Madison Madison, WI USA Head of laboratory http://oconnorgiles.molbio.wisc.edu Drosophila -Technology development
We are also developing genetic technologies for identifying and gaining genetic control of neuronal subtypes to determine their characterize their roles in neural circuits. Working with the laboratories of Jill Wildonger and Melissa Harrison, we recently adapted the CRISPR/Cas9 system for use in Drosophila. CRISPR is a novel technique that is revolutionizing genome engineering. Developed from bacteria where the CRISPR/Cas9 system functions in acquired immunity, CRISPR technology enables highly efficient and specific editing of targeted genomic sequences – opening the door to routine genome engineering. The many applications of CRISPR technology include modifying the genomes of model organisms to probe gene function, conferring disease resistance to agricultural organisms, and correcting disease-causing mutations in humans. We are capitalizing on this advance to develop novel genome engineering approaches that overcome current technological limitations to understanding neural circuits. Visit our flyCRISPR and flyCRISPR Optimal Target Finder sites for more details on our genome engineering work.
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April Pawluk University of California Berkeley Berkeley, CA USA Postdoctoral fellow http://rna.berkeley.edu/people.html @AprilPawluk Host-pathogens interaction
Bacteria and their cognate viruses, known as bacteriophages, are in a constant battle for survival. Among many mechanisms that bacteria possess to defend against bacteriophage infection, one of the most widespread and sophisticated is the CRISPR-Cas system. Setting CRISPR-Cas apart from other defence systems is the fact that it is an adaptive immunity system: one that can acquire the ability to target newly encountered invaders in a sequence-specific manner. Although much has been uncovered about the targeting mechanisms of CRISPR-Cas systems, very little is known about how they select and capture genetic snapshots of bacteriophages for later use as guides for the “seek and destroy” machinery. I leverage biochemical and structural biology approaches to investigate the CRISPR-Cas adaptation process in detail.
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Jennifer Phillips University of Oregon Eugene, OR USA Research Fellow http://zfin.org/ZDB-PERS-040915-1 @ClutchScience Zebrafish – Technology development
Our laboratory studies the molecular genetic basis of human diseases, particularly Usher syndrome, the leading cause of combined deafness and blindess, and other diseases of the eye and ear.
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Wenning Qin Biogen inc Cambridge, MA USA Director of Research https://www.biogen.com @wenningqin Mouse – Technology development
Wenning has been focusing on and exploring into genetic engineering technologies in her entire professional career. Her association includes Monsanto Biosciences, Pharmacia Corporation, Pfizer Incorporated and the Jackson Laboratory. She currently directs the Genetically Engineered Models group of Biogen, leveraging into genetic engineering to advance drug discovery pipeline for Biogen. Over the years, she acquired extensive knowledge and experience in design and creation of genetically engineered models, using random transgenesis, conventional gene targeting as well as CRISPR/Cas9 technology.
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Rakhi Rajan The University of Oklahoma Norman, OK USA Assistant Professor http://www.ou.edu/cas/chemistry/directory/faculty/rakhi-rajan.html RNA biology – Adaptive immunity
Protein-nucleic acid interactions are key to fundamental life processes such as DNA replication, transcription, recombination, and protein synthesis. Deciphering the mechanism of protein-nucleic acid interactions is invaluable for understanding human disease pathways and infections. The primary focus of my lab is to characterize protein-DNA/RNA interactions structurally, biochemically, and biophysically. The immediate emphasis is the study of the recently discovered bacterial and archaeal immune system, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR is an RNA-based adaptive immune system that inactivates foreign DNA/RNA entering the cell, based on the sequence similarity of small RNAs, called CRISPR RNA (crRNA) to the invading genetic element. The process requires several proteins called CRISPR associated (Cas) proteins. The CRISPR/Cas9 system has revolutionized the genome editing field due to the ease with which targeted double-stranded DNA breaks can be achieved in cells, using a guide RNA and Cas9 protein. The long-term goals of my laboratory are to understand the role of CRISPR/Cas system in pathogenicity and virulence of bacteria, characterize the mechanism of adaptation of bacteria to phage infection, and to determine the signaling mechanisms of the CRISPR/Cas system. We incorporate molecular biology, biochemistry, X-ray crystallography, and additional biophysical tools to characterize these protein-nucleic acid interactions.
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Dipali Sashital Iowa State University Ames, IA USA Assistant Professor http://www.sashitallab.org @dsashital RNA biology – Adaptive immunity
RNA-protein (RNP) complexes are central to many fundamental processes of gene regulation and genome maintenance in all kingdoms of life. The RNA components of these molecular machines often carry out diverse functions, acting as guide, template, scaffold, or catalyst. Despite this versatility, RNAs require protein partners to function, and the interactions that form between these components often dictate the overall activity of the RNP complex. Our lab is interested in understanding the molecular mechanisms underlying the function of RNPs from diverse cellular pathways. To that end, we combine a broad range of biochemical, structural and cellular tools to study RNA and protein structure, interactions and function.
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Nikki Shariat Gettysburg College Gettysburg, PA USA Assistant Professor https://sites.google.com/site/nikkishariat/home-1 RNA biology – Adaptive immunity
The Shariat Lab research interests are in prokaryote small RNA regulation and function, specifically in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). These elements are present in nearly half of all sequenced bacterial genomes and comprise several unique short sequences, called spacers, which are interspaced by conserved direct repeats. Spacers are derived from exogenous nucleic acids, such as bacteriophage genomes and plasmids. The spacers are transcribed into CRISPR RNAs (crRNAs), which are subsequently targeted to complementary nucleic acids, resulting in degradation of the target. Due to acquisition of new spacers, CRISPRs provide a remarkably dynamic adaptive immune system in both bacteria and archaea.
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Bettina Schmid Deutsches Zentrum fur Neurodegenerative Erkankungen Helmotz Germany Head of laboratory https://www.dzne.de/en/sites/munich/research-groups/schmid.html Zebrafish – Technology development
Our group uses the advantages of the zebrafish, Danio rerio, as an in vivo model system to address some of the unresolved questions in Alzheimer’s disease, Parkinson’s disease, Frontotemporal Lobar Degeneration (FTLD), and Amyotrophic lateral Sclerosis (ALS).
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Kimberley Seed University of California Berkeley Berkeley, CA USA Assistant Professor http://www.kimseedlab.com/#introduction Host-pathogens interaction
The ability of V. cholerae to prevent phage predation is critical for its evolutionary fitness and epidemic potential. In turn, as obligate bacterial parasites, phages must co-evolve to overcome this resistance or they will face extinction. Our research is aimed at understanding the bacterial immunity and opposing phage immune evasion strategies at play in this dynamic co-evolutionary arms race. We use comparative genomics and complementary molecular approaches to identify and experimentally validate such strategies in disease associated phage and V. cholerae isolates.
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Kaylene Simpson Peter McCallum Cancer Centre Melbourne Australia Associate Professor
High Throughput Screening – Technology Development
The Victorian Centre for Functional Genomics (VCFG) at Peter Mac offers biomedical researchers Australia-wide the ability to perform novel discovery-based functional interrogation all genes in the genome, or selected boutique collections using multiple platforms including CRISPR/cas9, small interfering RNA (siRNA), micro RNA (miRNA) and long non-coding RNA (lncRNA) and short hairpin RNA (shRNA).
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Joyce Van Eyck Cornell Univeristy Ithaca, NY USA Assistant Professor http://bti.cornell.edu/explore-bti/directory/joyce-van-eck/#research-overview Plant Biology (Tomato) – Technology Development
The focus of research in the Van Eck laboratory is biotechnological approaches to the study of gene function and crop improvement. For our studies, we apply several genetic engineering strategies to two major food crops: potato and tomato. The development of biotechnological techniques has made it possible to design and introduce gene constructs into plant cells and recover plants that express the introduced genes. Genes of interest to us have the potential to strengthen a plant’s resistance to disease, improve fruit characteristics, and enhance nutritional quality.
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Stineke Van Houte University of Exeter Exeter UK Research Fellow http://www.exeter.ac.uk/esi/people/researchandtechnical/van_houte/ Host-pathogens interaction
I am a biologist with a broad interest in host-parasite interactions, from an evolutionary, ecological and molecular perspective. Currently I work as a Marie-Curie fellow in the lab of Professor Angus Buckling on the evolution of immunity against virus infections in Pseudomonas bacteria. My PhD research at the Laboratory of Virology, Wageningen University (the Netherlands) focused on manipulation of host insect behaviour by baculoviruses, insect-specific viruses that cause lethal disease in caterpillars.
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Leslie Vosshall The Rockfeller Univeristy New York, NY USA Head of laboratory http://vosshall.rockefeller.edu @pollyp1 Insect – Technology development
The overall goal of work in our laboratory is to understand how complex behaviors are modulated by external chemosensory cues and internal physiological states. The lab takes a multi-disciplinary approach spanning cell biology, genetics, neurobiology and behavior. Our early focus has been to study how the brain interprets olfactory signals in the environment that signal food, danger, or potential mating partners. We have been studying these problems in three model organisms: the fly, the mosquito and the human. The majority of the early work in the laboratory was carried out in the genetically tractable vinegar fly, Drosophila melanogaster, which displays a rich repertoire of chemosensory behaviors despite having a nervous system with only 100,000 neurons. In this animal, we have studied the functional neuroanatomy of the olfactory system, how this system perceives sex pheromones, and the structure and function of the insect odorant receptors.
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Kan Wang Iowa State University Agron,IA USA Professor http://www.agron.iastate.edu/personnel/userspage.aspx?id=266 Plant biology (Maize) – Technology development
As the rapid development in plant genomics research identifies more genes, their functional analysis relies on strategies such as complementation, overexpression, or gene silencing. Plant genetic transformation is a critical technology required in the application of these strategies.
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Rachel Whitaker University of Illinois at Urbana Champaign Urbana, IL USA Associate Professor http://www.life.illinois.edu/whitaker/ Evolution and Ecology – Adaptive immunity
My lab combines population genomics with laboratory-based genetic and genomic experimental techniques to study the evolutionary ecology of microbial populations. We take a comparative approach, examining interactions within and between species using wild strains from natural populations isolated across spatial and temporal scales. Currently we are working on two critical forces that define the evolutionary process in all organisms: host-virus co-evolution and recombinational gene flow. We have a particular interest in how the unique biology of organisms in the Archaeal domain is reflected in genome architecture and how the CRISPR-Cas immune system functions in microbial populations.
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Susan Woods University of Adelaide Adelaide Australia Senior Research Fellow https://researchers.adelaide.edu.au/profile/susan.woods#career Cancer biology – Technology Development
Susan’s current project focuses on colorectal cancer. This is the second most common cancer type in Australia, costing us over $1 billion dollars annually. There are minimal effective treatments for advanced disease. The lab has recently identified a new stem cell that gives rise to a layer of cells that support the intestinal lining. We are investigating whether similar support cells can promote the formation of colorectal cancer from cells lining the intestine, and if we can prevent it using a new therapeutic approach.
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Luhan Yang eGenesis Cambridge, MA USA Co-founder and CSO http://www.egenesisbio.com/founding-team.html Biotech – Technology development
Luhan is leading the effort to eradicate PERVs from the porcine genome and engineer human compatibility in porcine cells. She previously developed the highly programmable genome-engineering tool, CRISPR/Cas9, for use in mammalian cells, and pioneered the first isogenic human stem cell lines to model human diseases at the tissue level. She was named among the “30 Under 30” in Science and Healthcare by Forbes Magazine (2014) and was a laureate of the “Young Entrepreneur Initiative” competition (2014). Luhan holds B.S. degrees in Biology and Psychology from Peking University and a Ph.D. in Human Biology and Translational Medicine from Harvard Medical School.
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Yan Zhang University of Michigan Ann Arbor, MI USA Assistant Professor https://medicine.umich.edu/dept/biochem/yan-zhang-p RNA biology – Technology development
CRISPR-Cas is a RNA-guided, genetic interference pathway in prokaryotes that enables acquired immunity against invasive nucleic acids. Nowadays, CRISPRs also provide formidable tools for facile, programmable genome engineering in eukaryotes. Cas9 proteins are the “effector” endonucleases for CRISPR interference; and have recently begun to be also recognized as important players in other aspects of bacterial physiology (e.g. acquisition of new spacers into CRISPRs, endogenous gene regulation, and microbial pathogenesis, etc.).My laboratory is broadly interested in CRISPR biology and mechanism. We will use Neisseria species as our model system, and E. coli and human cells as additional platforms. We employ complementary biochemical, microbiological, genetic and genomic approaches. We are also interested in working with the broader scientific community to develop and apply novel CRISPR-based tools to tackle diverse biological questions.

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