Archive for the ‘CRISPR/Cas9 & Gene Editing’ Category

National Academy of Sciences for work in chemical sciences: Jennifer Doudna, University of California, Berkeley

Reporter: Aviva Lev-Ari, PhD, RN



National Academy of Sciences awards for Raghavendra, Doudna

Prasad Raghavendra and Jennifer Doudna received awards this week from the National Academy of Sciences for work in computer science and chemical sciences, respectively.

Prasad Raghavendra, an associate professor of electrical engineering and computer science, and Jennifer Doudna, a professor of molecular and cell biology and of chemistry, were honored this week by the National Academy of Sciences for their innovative body of research.

Raghavendra shared the inaugural Michael and Sheila Held Prize with David Steurer, a professor of theoretical computer science at ETH Zurich, for “revolutionary contributions to the understanding of optimization and complexity in computer science, work that has relevance for solving the most difficult and intractable of computing problems.” The winners will share the $100,000 prize.

Doudna, a Howard Hughes Medical Institute investigator, received the 2018 NAS Award in Chemical Sciences for “pioneering discoveries on how RNA can fold to function in complex ways” and the invention, with Emmanuelle Charpentier, of the CRISPR-Cas9 gene-editing technology.

The winners will be honored in a ceremony on Sunday, April 29, during the National Academy of Sciences’ 155th annual meeting.

Raghavendra’s prize, awarded this year for the first time, was made possible through a bequest from the estate of Michael and Sheila Held. Doudna’s award, established in 1978 and currently supported by the Merck Company Foundation, is accompanied by a medal and a $15,000 prize.

Previous winners of the NAS Award in Chemical Sciences include Paul Alivisatos, a professor of chemistry and UC Berkeley’s executive vice chancellor and provost, chemistry professors emeritus Gabor Somorjai and Robert Bergman, and former chemistry professor Carolyn Bertozzi, who is now at Stanford University.

Another former UC Berkeley faculty member, James Allison, received the NAS’s 2018 Jessie Stevenson Kovalenko Medal “for important medical discoveries related to the body’s immune response to tumors.” He is now at the University of Texas MD Anderson Cancer Center. All are among 18 awards to 21 scientists announced this week.

National Academy of Sciences announcement




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CRISPR on TED Ideas worth spreading – Ellen Jorgensen

Reporter: Aviva Lev-Ari, PhD, RN

On same webpage see other CRISPR Talk on TED on the right hand side of the webpage



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CRISPR snips a strand of DNA – Visualization of the Process

Reporter: Aviva Lev-Ari, PhD, RN


Watch what it actually looks like when CRISPR snips a strand of DNA


Molecular animations are an essential way to demystify and explain complex biological systems. Through the use of stunning imagery and attention to detail, Visual Science and Skoltech have captured the dynamic mechanisms of CRISPR-Cas proteins and their use as research tools.

 Jennifer Doudna, Professor of the Depts. of Molecular and Cell Biology and Chemistry at the UC Berkeley, Executive Director of the Innovative Genomics Institute

You can watch the animation, created by biologists at Russia’s Skoltech Institute and the Visual Science organization, below or at the latter’s website:

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

Curator: Aviva Lev-Ari, PhD, RN



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


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) 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.”



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.



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.


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.

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.”



Role of Immune system in gene therapy using CRISPR Cas9


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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


UPDATED on 10/10/2017

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

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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.

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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




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.

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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.


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

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

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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

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


(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.


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
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.


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.


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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