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

CRISPR companies calling for article retraction from Nature Methods – If the same or similar sequence of letters appears elsewhere in the genome, that can result in an unintentional or off-target edit – Concerns of Harm caused by Gene Editing using CRISPR-Cas9, 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 companies calling for article retraction from Nature Methods – If the same or similar sequence of letters appears elsewhere in the genome, that can result in an unintentional or off-target edit – Concerns of Harm caused by Gene Editing using CRISPR-Cas9

 

Reporter: Aviva Lev-Ari, PhD, RN

Storm around the call for “Nature Methods editorial board to retract this paper.”

A spokesperson at Springer Nature, which publishes Nature Methods, said the organization had received “a number of communications” already about the paper. “We are carefully considering all concerns that have been raised with us and are discussing them with the authors,” the journal said. Vinit Mahajan of Stanford University, who was the paper’s senior author, did not immediately respond to a request for comment. Another author, Alexander Bassuck of the University of Iowa, said he was traveling and unable to respond immediately.

 

The paper, titled

Unexpected mutations after CRISPR–Cas9 editing in vivo, triggered a rash of negative headlines after claiming the gene-editing tool caused widespread and unpredictable havoc in the genomes of edited mice, introducing hundreds of unintended errors.

The stock market value of Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics, which together have raised more than $1 billion to pursue CRISPR treatments, all fell sharply on the news.

CRISPR technology is widely touted as a revolutionary new means of easily altering DNA. But its promise is being exaggerated in media reports, including some that claim it will cure all genetic disease and solve the world’s food problems with superplants.

CRISPR can be programmed to cut specific sequences of DNA letters, thereby correcting or changing genes. While this versatility is what makes it powerful, if the same or similar sequence of letters appears elsewhere in the genome, that can result in an unintentional or off-target edit. Concern over the technique’s potential side effects is widely shared, even by some of its inventors.

The fear is that planned medical treatments using CRISPR could prove dangerous. A single erroneous cut could be disastrous for patients if it lands in a vital gene. Fifteen years ago, pioneering experiments in gene therapy were set back when unintentional genetic changes caused cancer in some children. Many scientists believe careful programming can eliminate most of the risk.

The ease of use of CRISPR means nearly any lab can try it. In China, some human experiments have already begun. The rush to use the method is part of what’s creating anxiety, since it makes mistakes more likely. Editas recently postponed its own planned study of CRISPR to correct an eye disease until next year.

According to Intellia, however, the authors showed “disregard” for what’s already known about CRISPR. “It is clear the authors are not experts on the CRISPR Cas9, whole genome sequencing, nor basic genetics. Their claim of ‘unexpected mutations’ clearly demonstrates their lack of scientific acumen around this topic,” the company said.

SOURCE

Gene-Editing Companies Hit Back at Paper That Criticized CRISPR

Report that suggested CRISPR is too dangerous to use as a drug was wrong, say biotech companies.

Jun 9, 2017

EmTech: Risks of Gene-Editing Drugs Need Study, Pioneer Warns

One of the inventors of gene editing says scientists should proceed cautiously before testing it in people.

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Human gene editing continues to hold a major fascination within a biomedical and biopharmaceutical industries. It’s extraordinary potential is now being realized but important questions as to who will be the beneficiaries of such breakthrough technologies remained to be answered. The session will discuss whether gene editing technologies can alleviate some of the most challenging unmet medical needs. We will discuss how research advances often never reach minority communities and how diverse patient populations will gain access to such breakthrough technologies. It is widely recognize that there are patient voids in the population and we will explore how community health centers might fill this void to ensure that state-of-the-art technologies can reach the forgotten patient groups . We also will touch ethical questions surrounding germline editing and how such research and development could impact the community at large.

Please follow LIVE on TWITTER using the following @ handles and # hashtags:

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@pharma_BI

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CRISPR cuts turn gels into biological watchdogs, 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

Update 6/11/2020

CRISPR-IL used to develop next-gen genome editing products

  1. Haifa-based Pluristem Therapeutics is a regenerative medicine company that plans to develop next-generation multi-species genome editing products for human, plant and animal DNA that could improve work done in the pharma, agriculture and aquaculture industries.
  2. The CRISPR-IL consortium includes Sheba Medical Center and Schneider Children’s Medical Center, Bar-Ilan University, Ben-Gurion University of the Negev, Hebrew University of Jerusalem, the Weizmann Institute of Science, IDC Herzliya and Tel-Aviv University.
  3. This consortium is also joined by Pluristem Therapeutics, which plans to bring together a team of multi-disciplinary experts to develop artificial intelligence  based end-to-end genome-editing solutions.
  4. The genome editing product designed by Pluristerm should improve existing technology.
  5. The project also includes “the computational design of on-target DNA modification, with minimal accidental, off-target modifications, improve modification efficiency.
  6. The product provides an accurate measuring tool to ensure the desired modification.

SOURCE

https://www.jpost.com/health-science/pluristem-joins-crispr-il-to-develop-next-gen-genome-editing-products-630337?utm_source=ActiveCampaign

CRISPR cuts turn gels into biological watchdogs

Reporter: Irina Robu, PhD

Genome editing if of significant interest in the prevention and treatment of human diseases including single-gene disorders such as cystic fibrosis, hemophilia and sickle cell disease. It also shows great promise for the prevention and treatment of diseases such as cancer, heart disease, mental illness and human immunodeficiency virus infection. However, ethical concerns arise when genome editing, using technologies such as CRISPR-Cas9 is used to alter human genomes.

James Collins, bioengineer at MIT and his team worked with water-filled polymers that are held together by strands of DNA, known as DNA hydrogels. To alter the properties of these materials, these scientists turned to a form of CRISPR that uses a DNA-snipping enzyme called Cas12a, which can be programed to recognize a specific DNA sequence. The enzyme then cuts its target DNA strand, then severs single strands of DNA nearby. This property lets scientists to build a series of CRISPR-controlled hydrogels encapsulating a target DNA sequence and single strands of DNA, which break up after Cas12a identifies the target sequence in a stimulus. The break-up of the single DNA strands activates the hydrogels to change shape or completely dissolve, releasing a payload.

According to Collins and his team, the programmed hydrogels will release enzymes, small molecules and human cells as part of a smart therapy in response to stimuli. However, in order to make it a smart therapeutic, the researchers in collaboration with Dan Luo, bioengineer at Cornell University placed the CRISPR- controlled hydrogels into electric circuits. The circuit is switched off in response to the detection of the genetic material of harmful pathogens such as Ebola virus and methicillin-resistant Staphylococcus aureus. The team used these hydrogels to develop a prototype diagnostic tool that sends a wireless signal to identify Ebola in lab samples.

Yet, it is evident that these CRISPR-controlled hydrogels show great potential for the prevention and treatment of diseases.

SOURCE

https://www.nature.com/articles/d41586-019-02542-3?utm_source=Nature+Briefing

 

 

 

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At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells., 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

At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells.

Reporter: Aviva Lev-Ari, PhD, RN

 

Targeted exchange using the CRISPR-Cas9 gene scissors

The problem with conventional methods is that the genetic information for the new receptors is randomly inserted into the genome. This means that T cells are produced with both new and old receptors or with receptors having one old and one new chain. As a result, the cells do not function as effectively as physiological T cells and are also controlled differently. Moreover, there is a danger that the mixed chains could trigger dangerous side effects (Graft-versus-Host Disease, GvHD).

“Using the CRISPR method, we’ve been able to completely replace the natural receptors with new ones, because we’re able to insert them into the very same location in the genome. In addition, we’ve replaced the information for both chains so that there are no longer any mixed receptors,” explains Kilian Schober, who is a lead author of the new study along with his colleague Thomas Müller.

Near-natural properties

Thomas Müller explains the advantages of the modified T cells: “They’re much more similar to physiological T cells, yet they can be changed flexibly. They’re controlled like physiological cells and have the same structure, but are capable of being genetically modified.“ The scientists have demonstrated in a cell culture model that T cells modified in this way behave nearly exactly like their natural counterparts.

“Another advantage is that the new method allows multiple T cells to be modified simultaneously so that they’re able to recognize different targets and can be used in combination. This is especially interesting for cancer therapy, because tumors are highly heterogeneous,” Dirk Busch adds. In the future, the team plans to investigate the new cells and their properties in preclinical mouse models, an important step in preparing for clinical trials with humans.

Original Publication

Kilian Schober, Thomas R. Müller, Füsun Gökmen, Simon Grassmann, Manuel Effenberger, Mateusz Poltorak, Christian Stemberger, Kathrin Schumann, Theodore L. Roth, Alexander Marson and Dirk H. Busch: Orthotopic replacement of T-cell receptor ɑ- and β-chains with preservation of near-physiological, Nature Biomedical Engineering, June 12, 2019, DOI: 10.1038/s41551-019-0409-0

 

SOURCE

https://www.tum.de/nc/en/about-tum/news/press-releases/details/35560/

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@BroadInstitute a shift from Permanently editing DNA to Temporarily revising RNA – An approach with promise for addressing the risk of developing Alzheimer’s by deactivating APOE4 – RESCUE: RNA Editing for Specific C to U Exchange, the platform builds on REPAIR: RNA Editing for Programmable A to I

Reporter: Aviva Lev-Ari, PhD, RN

2.1.3.14

UPDATED on 8/30/2021

Compact RNA editors with small Cas13 proteins

Abstract

CRISPR–Cas13 systems have been developed for precise RNA editing, and can potentially be used therapeutically when temporary changes are desirable or when DNA editing is challenging. We have identified and characterized an ultrasmall family of Cas13b proteins—Cas13bt—that can mediate mammalian transcript knockdown. We have engineered compact variants of REPAIR and RESCUE RNA editors by functionalizing Cas13bt with adenosine and cytosine deaminase domains, and demonstrated packaging of the editors within a single adeno-associated virus.

SOURCE

Kannan, S., Altae-Tran, H., Jin, X. et al. Compact RNA editors with small Cas13 proteins. Nat Biotechnol (2021). https://doi.org/10.1038/s41587-021-01030-2

https://www.nature.com/articles/s41587-021-01030-2

2.1.3.14   @BroadInstitute a shift from Permanently editing DNA to Temporarily revising RNA – An approach with promise for addressing the risk of developing Alzheimer’s by deactivating APOE4 – RESCUE: RNA Editing for Specific C to U Exchange, the platform builds on REPAIR: RNA Editing for Programmable A to I, 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 RNA editors converted “the nucleotide base adenine to inosine, or letters A to I. Zhang and colleagues took the REPAIR fusion and evolved it in the lab until it could change cytosine to uridine, or C to U.”
  • Using Cas13, Zhang’s team was able to take the APOE4 gene — believed to carry the added risk of spurring Alzheimer’s — and changed it to a benign APOE2.

RNA-guided DNA insertion with CRISPR-associated transposases

Science  05 Jul 2019:
Vol. 365, Issue 6448, pp. 48-53
DOI: 10.1126/science.aax9181
SOURCE

Other related articles on CRISPR derived Gene Editing for Gene Therapy published in this Open Access on Online Scientific Journal include the following:

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Forthcoming 12/2019, Volume Two

by

Prof. Marcus W. Feldman, PhD, Editor, Stanford University

Prof. Stephen J. Williams, PhD, Editor, Temple University

and Aviva Lev-Ari, PhD, RN, Editor, LPBI Group 

 

Part 2: CRISPR for Gene Editing and DNA Repair

2.1 The Science – 77 articles

2.2 Technologies and Methodologies – 27 articles

2.3 Clinical Aspects – 9 articles

2.4 Business and Legal – 18 articles

Series B: Frontiers in Genomics Research

 

  • VOLUME 1: Genomics Orientations for Personalized Medicine. On Amazon.com since 11/23/2015

http://www.amazon.com/dp/B018DHBUO6

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FIVE Forthcoming Books on CRISPR in 2019-2020: Flooded market or CRISPR-fatigued readers – Not to Worry !!!!!

Author: Aviva Lev-Ari, PhD, RN

 

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

Date: Thursday, July 4, 2019 at 8:39 PM

To: <damian.garde@statnews.com>

Cc: Marcus W Feldman <mfeldman@stanford.edu>, “Stephen Williams, PhD” <sjwilliamspa@comcast.net>, Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>, Gail Thornton <gailsthornton@yahoo.com>

Subject: Regarding your article: Walter Isaacson is writing a book about CRISPR. He’s got company —>>>>>> e-mail from AVIVA LEV-ARI, PhD, RN, EDITOR-in-CHIEF PharmaceuticalIntelligence.com

attn:

damian.garde@statnews.com

 

Dear Mr. Grade,

 

In your article

Walter Isaacson is writing a book about CRISPR. He’s got company

By DAMIAN GARDE @damiangarde 7/2/2019

https://www.statnews.com/2019/07/02/walter-isaacson-crispr-books/?utm_source=STAT+Newsletters

 

you mention the following FOUR forthcoming books on CRISPR:

 

  • Walter Isaacson, the famed biographer, is among a number of authors working on books about gene editing and CRISPR.

Title TBD, Year of Publication and Publisher, TBD

 

  • Kevin Davies

“Editing Mankind,”

Forthcoming 2020, Pegasus

 

  • Michael Specter, Stanford University

Title TBD

Forthcoming 202?, Crown Publishing Group

 

Altered Inheritance – CRISPR and the Ethics of Human Genome Editing

Harvard University Press

HARDCOVER

$24.95 • £19.95 • €22.50

ISBN 9780674976719

Publication Date: 09/17/2019

 

I wish to bring to your attention the following book on Genomics that has in its Part 2 over 100 articles on CRISPR.

  • This book is part of a Series of 16 Books in Medicine

https://lnkd.in/ekWGNqA

available on amazon.com

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Forthcoming 12/2019, Volume Two

by

Prof. Marcus W. Feldman, PhD, Editor, Stanford University

Prof. Stephen J. Williams, PhD, Editor, Temple University

and Aviva Lev-Ari, PhD, RN, Editor, LPBI Group 

 

Part 2: CRISPR for Gene Editing and DNA Repair

2.1 The Science – 77 articles

2.2 Technologies and Methodologies – 27 articles

2.3 Clinical Aspects – 9 articles

2.4 Business and Legal – 18 articles

 

It will be appreciated if you will write a follow up to your 7/2/2019 article to cover this volume (Eight Parts) and all our 16 volumes, BioMed e-Series, 96,000 Page Downloads !!

 

 

SOURCE for Damian Grade’s article in StatNews:

Walter Isaacson is writing a book about CRISPR. He’s got company

By DAMIAN GARDE @damiangarde 7/2/2019

National Biotech Reporter

Damian covers biotech and writes The Readout newsletter.

damian.garde@statnews.com

https://www.statnews.com/2019/07/02/walter-isaacson-crispr-books/?utm_source=STAT+Newsletters

 

Looking forward to hearing from you

Sincerely, yours,

 

Aviva Lev-Ari, PhD, RN

Director & Founder

https://lnkd.in/eEyn69r

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

Editor-in-Chief

http://pharmaceuticalintelligence.com

e-Mail: avivalev-ari@alum.berkeley.edu

(M) 617-775-0451

https://cal.berkeley.edu/AvivaLev-Ari,PhD,RN

SkypeID: HarpPlayer83          LinkedIn Profile        Twitter Profile

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Optimization of CRISPR Gene Editing with Gold Nanoparticles

Reporter: Irina Robu, PhD

The CRISPR-Cas9 gene editing system has been welcomed as a hopeful solution to a range of genetic diseases, but the expertise has proven hard to deliver into cells. One plan is to open the cell membrane using an electric shock, but that can accidentally kill the cell. Another is to use viruses as couriers. Problem is, viruses can cause off-target side effects.

CRISPR-Cas9 is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of DNA sequence. It is faster, cheaper and more accurate than previous techniques of editing DNA and can have a wide range of potential applications.

The CRISPR-Cas9 system consists of two key molecules that introduce a change into the DNA. One is an enzyme called Cas9 which acts as a pair of molecular scissors that can cut the two strands of DNA at a specific location in the genome where bits of DNA can be added or removed. The other one, is a piece of RNA which consists of a small piece of pre-designed RNA sequence located within a longer RNA scaffold. The scaffold part binds to the DNA and pre-designed sequence which contains Cas9. The RNA sequence is designed to find and locate specific sequence in the DNA. The Cas9 trails the guide RNA to the same location in the DNA sequence and makes a cut across both strands of DNA. At this point the cell distinguishes that the DNA is damaged and tries to repair it.

Researchers at Fred Hutchinson Cancer Research Center published new findings in Nature Materials suggested an alternative delivery method such as gold nanoparticles. The gold nanoparticles are packed with all the CRISPR components necessary to make clean gene edits. When the gold nanoparticles were tested in lab models of inherited blood disorders and HIV, between 10% and 20% of the targeted cells were effectively edited, with no toxic side effects.

The researchers use gold nanoparticles to deliver CRISPR to blood stem cells. Each gold nanoparticle contains four CRISPR components, including the enzyme needed to make the DNA cuts. But Fred Hutchinson researchers chose Cas12a, which they believed would lead to more efficient edits. Plus, Cas12a only needs one molecular guide, while Cas9 requires two.

In one experiment, they sought to disturb the gene CCR5 to make cells resistant to HIV. In the second, they created a gene mutation that can protect against blood disorders, including sickle cell disease. They observed the cells encapsulated the nanoparticles within six hours and began the gene-editing process within 48 hours. In mice, gene editing peaked eight weeks after injection, and the edited cells were still in circulation 22 weeks after the treatment.

Researchers at Fred Hutchinson are now working on improving the efficiency of the gold-based CRISPR delivery system so that 50% or more of the targeted cells are edited and are also looking for a commercial partner to bring the technology to clinical phase in the next few years.

SOURCE

https://www.fiercebiotech.com/research/fred-hutch-team-uses-gold-nanoparticles-to-improve-crispr-gene-editing

 

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Breakthrough in Gene Editing CRISPR–Cas systems: First example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair, 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

Breakthrough in Gene Editing CRISPR–Cas systems: First example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

 

Reporter: Aviva Lev-Ari, PhD, RN

 

CRISPR alternatives for editing genes without cutting: CRISPR 12, 12a, 13, 14 – Alternative Techniques to CRISPR/Cas9

 

  • Alternative to CRISPR/Cas9 – CAST (CRISPR-associated transposase) – A New Gene-editing Approach for Insertion of Large DNA Sequences into a Genome developed @BroadInstitute @MIT @Harvard

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/06/11/alternative-to-crispr-cas9-cast-crispr-associated-transposase-a-new-gene-editing-approach-for-insertion-of-large-dna-sequences-into-a-genome-developed-broadinstitute-mit-harvard/

 

  • Vertex Pharmaceuticals agreed to pay $420 million to acquire Exonics and to expand its partnership with CRISPR Therapeutics. The deal sets in motion a planto use CRISPR to treat Duchenne muscular dystrophy and myotonic dystrophy type 1.

 

  • In May, a team at the Fred Hutchinson Cancer Research Center described a method developed there to use gold nanoparticles to carry CRISPR components into cells and to use the Cas12a enzyme to make cleaner cuts than Cas9 typically does.

 

  • A UC Berkeley spinoff, GenEdit, is also developing a gold-based CRISPR system.

 

  • Other recently proposed ideas for improving CRISPR include attaching a hairpin-like guide to RNA to improve the accuracy of DNA cuts and adding an on-off switch to Cas9 enzymes to ensure they can’t make edits anywhere other than the targeted sites.

 

  • The next step for Sternberg’s team at Columbia is to test the INTEGRATE technology in mammalian cells. They believe the technique could eventually be applied to a variety of products, such as gene therapies and engineered crops.

 

Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration

Abstract

Conventional CRISPR–Cas systems maintain genomic integrity by leveraging guide RNAs for the nuclease-dependent degradation of mobile genetic elements, including plasmids and viruses. Here we describe a remarkable inversion of this paradigm, in which bacterial Tn7-like transposons have co-opted nuclease-deficient CRISPR–Cas systems to catalyze RNA-guided integration of mobile genetic elements into the genome. Programmable transposition of Vibrio cholerae Tn6677 in E. coli requires CRISPR- and transposon-associated molecular machineries, including a novel co-complex between Cascade and the transposition protein TniQ. Donor DNA integration occurs in one of two possible orientations at a fixed distance downstream of target DNA sequences, and can accommodate variable length genetic payloads. Deep sequencing experiments reveal highly specific, genome-wide DNA integration across dozens of unique target sites. This work provides the first example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

 SOURCE

A CRISPR alternative for editing genes without cutting

Scientists at Columbia University’s Vagelos College of Physicians and Surgeons are now proposing an alternative gene-editing system—one that sidesteps the need for DNA cutting altogether.

The researchers are using a “jumping gene,” or transposon, from a bacterium called Vibrio cholerae. The transposon is able to insert itself into different regions of the genome and can be programmed to carry any DNA sequence to any site. Therefore their technology, which they dubbed INTEGRATE, acts less like molecular scissors and more like molecular glue, they explained in the journal Nature.

“Rather than introduce DNA breaks and rely on the cell to repair the break, INTEGRATE directly inserts a user-defined DNA sequence at a precise location in the genome, a capability that molecular biologists have sought for decades,” said senior author Sam Sternberg, Ph.D., assistant professor of biochemistry and molecular biophysics at Columbia, in a statement. Sternberg recently joined Columbia after a stint working in the lab of CRISPR pioneer Jennifer Doudna at the University of California, Berkeley.

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Laboratory for Genomics Research (LGR) to be established by GSK ($67M investment in 5 years) at UC, Berkeley/UCSF to be lead by Prof. Jennifer Doudna focusing on immunology, oncology, and neuroscience disease-causing gene mutations and development of new technologies using CRISPR to accelerate new drug discovery

 

Reporter: Aviva Lev-Ari, PhD, RN

 

GlaxoSmithKline, UC’s Doudna Establish $67M Genomics, CRISPR Research Lab

Jun 13, 2019   |  staff reporter

Save for later

 

NEW YORK (GenomeWeb) – Drug company GlaxoSmithKline announced today that it will establish a laboratory for CRISPR technologies as part of a five-year collaboration with University of California researchers.

The new Laboratory for Genomics Research (LGR) will investigate disease-causing gene mutations and develop new technologies using CRISPR to accelerate the discovery of new drugs, with a focus on immunology, oncology, and neuroscience. The LGR will receive up to $67 million in funding over the five-year collaboration period, including facilities for 24 full-time university employees funded by GSK, plus up to 14 full-time GSK employees, the company said. GSK’s artificial intelligence and machine learning group will also aid in building any necessary bioinformatics pipelines. The laboratory will be based near the University of California, San Francisco’s Mission Bay campus.

The LGR aims to automate existing CRISPR approaches so that this work can be done at scale. Ultimately, the lab’s goal is to deepen researchers’ understanding of genetics and discover new drug targets. They’re also aiming to create next-generation technologies for the pharmaceutical industry, GSK added.

The LGR will also serve as a resource for investigators at both UCSF and the University of California, Berkeley who can access and use its technology to answer their own research questions and to develop new tools.

The LGR was developed by Berkeley professor and CRISPR expert Jennifer Doudna, UCSF Professor Jonathan Weissman, and GSK CSO and President of R&D Hal Barron.

“Over the last seven years, CRISPR has transformed academic research, but until the LGR, we haven’t had a focused effort to catalyze the kind of research we know will lead to new innovation using this CRISPR tool,” Doudna said in a statement. “LGR is about building that space where creative science is partnered with the development of robust technology that will help develop tomorrow’s drugs. I think we’re going to be able to do science that none of us can even imagine today.”

The collaboration will be governed by a Joint Steering Committee with equitable UC and GSK representation, with additional joint sub-committees covering patents, scientific, and project management, GSK noted. Doudna and Weissman will sit on the committee along with GSK’s new head of functional genomics, Chris Miller.

“One of our key goals is to advance the field overall and make these tools as broadly available as possible,” Weissman added in the statement. “The LGR screening center will enable labs at UCSF and Berkeley, and having access to it will give our scientists opportunities to advance their research in ways that would be very hard for them to do in their own labs.”

 

ADDITIONAL ARTICLES in GenomeWeb

SOURCE

https://www.genomeweb.com/business-news/glaxosmithkline-ucs-doudna-establish-67m-genomics-crispr-research-lab#.XQKQ8tNKgcg

 

Other related articles published in this Open Access Online Scientific Journal include the following 156 articles:

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

 

 

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Alternative to CRISPR/Cas9 – CAST (CRISPR-associated transposase) – A New Gene-editing Approach for Insertion of Large DNA Sequences into a Genome developed @BroadInstitute @MIT @Harvard, 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

Alternative to CRISPR/Cas9 – CAST (CRISPR-associated transposase) – A New Gene-editing Approach for Insertion of Large DNA Sequences into a Genome developed @BroadInstitute @MIT @Harvard

Reporter: Aviva Lev-Ari, PhD, RN

 

A new gene-editing CAST member

In Science, a team led by Jonathan Strecker, Alim Ladha, and core institute member Feng Zhang reports a new gene-editing approach that can precisely and efficiently insert large DNA sequences into a genome. The system, called CRISPR-associated transposase (CAST), is a completely new platform to integrate genetic sequences into cellular DNA, addressing a long-sought goal for precision gene editing. The team molecularly characterized and harnessed the natural CAST system from cyanobacteria, also unveiling a new way that some CRISPR-associated systems perform in nature: not to protect bacteria from viruses, but to facilitate the spread of transposon DNA. Check out more in coverage from STAT and New Scientist.

SOURCE

https://www.broadinstitute.org/news/research-roundup-june-7-2019

 

RNA-guided DNA insertion with CRISPR-associated transposases

Science  06 Jun 2019:
eaax9181
DOI: 10.1126/science.aax9181

Abstract

CRISPR-Cas nucleases are powerful tools to manipulate nucleic acids; however, targeted insertion of DNA remains a challenge as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase (CAST) from cyanobacteria Scytonema hofmanni which consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60-66 bp downstream of the protospacer. ShCAST integrates DNA into unique sites in the E. coli genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.

 

SOURCE

https://science.sciencemag.org/content/early/2019/06/05/science.aax9181

 

Other related articel published in thies Open Access Online Scientific Journal, include:

Breakthrough in Gene Editing CRISPR–Cas systems: First example of a fully programmable, RNA-guided integrase and lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/06/13/breakthrough-in-gene-editing-crispr-cas-systems-first-example-of-a-fully-programmable-rna-guided-integrase-and-lays-the-foundation-for-genomic-manipulations-that-obviate-the-requirements-for/

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