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Home » AstraZeneca collaborates to use CRISPR technology

AstraZeneca collaborates to use CRISPR technology

January 30, 2015
CenterWatch Staff

AstraZeneca has announced four research collaborations aimed at harnessing the power of CRISPR, a pioneering genome-editing technique, across its entire discovery platform in the company’s key therapeutic areas. The four research collaborations are with the Wellcome Trust Sanger Institute, Cambridge, U.K.; the Innovative Genomics Initiative, California; Thermo Fisher Scientific, Waltham, Mass.; and the Broad Institute/Whitehead Institute, Cambridge, Mass. The technology will allow AZ to identify and validate new drug targets in preclinical models that closely resemble human disease.

AZ will share cell lines and compounds with its partners and work with them to publish findings of its application of CRISPR technology in peer-reviewed journals, contributing to broader scientific progress in the field. The collaborations complement AZ’s in-house CRISPR program and will build on the company’s open innovation approach to R&D.

CRISPR (clustered regularly interspaced short palindromic repeats) is a genome-editing tool, which allows scientists to make changes in specific genes far faster and in a much more precise way than ever before. The technology has two components—a homing device to a specific section of DNA (guide-RNA) and enzymatic “scissors” that cut DNA (Cas9 nuclease).

In the cell nucleus, the guide-RNA sequence directs the Cas9 nuclease to cause double-stranded breaks in the target DNA sequence. By harnessing the cell’s own DNA-repair apparatus, the gene being targeted can be altered either by deleting it, adding nucleotides to it or by turning its activity on or off. In contrast to previous genome-editing techniques, such as zinc-finger nucleases and TALENs, CRISPR is easier to handle in the laboratory.

Dr. Mene Pangalos, executive vice president, innovative medicines and early development, AZ, said, “CRISPR is a simple yet powerful tool that enables us to manipulate genes of potential importance in disease pathways and examine the impact of these modifications in a highly precise way.

Under the terms of the collaboration with the Wellcome Trust Sanger Institute, research will focus on deleting specific genes relevant to cancer, cardiovascular, metabolic, respiratory, autoimmune and inflammatory diseases and regenerative medicine to understand their precise role in these conditions. AZ will provide cell lines that can be targeted using the Sanger Institute’s collection of genome-wide CRISPR guide-RNA libraries to generate populations of cells in which defined genes are switched off. Genes will subsequently be identified by next-generation sequencing and cell populations tested to validate the effects of a given gene on a wide range of physical and biological traits.

The Wellcome Trust Sanger Institute is a genome center. Through its ability to conduct research at scale, it is able to engage in long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programs and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

“The Sanger Institute’s guide-RNA library enables researchers to target genes with incredible specificity,” said Dr. Kosuke Yusa, member of faculty at the Sanger Institute. “CRISPR has transformed the way we study the behavior of cells and now the application of this powerful technology to the search for effective drugs has the potential to benefit patients.”

The Innovative Genomics Initiative (IGI) is a joint venture between the University of California, Berkeley and University of California, San Francisco. The research collaboration will focus on either inhibiting (CRISPRi) or activating (CRISPRa) genes to understand their role in disease pathology. The IGI and AZ will work closely together to identify and validate gene targets relevant to cancer, cardiovascular, metabolic, respiratory, autoimmune and inflammatory diseases and regenerative medicine to understand their precise role in these conditions.

Under the terms of the collaboration with Thermo Fisher Scientific, AZ will receive RNA-guide libraries that target individual known human genes and gene families. AZ can screen these guides against cell lines to identify new disease targets.

“Through this research collaboration with AstraZeneca, Thermo Fisher is helping to accelerate access to cutting edge genome-editing applications for next generation drug discovery. Enabling more relevant disease models will improve target identification and translation to therapeutics,” said Dr. Jon Chesnut, director of Synthetic Biology R&D at Thermo Fisher Scientific.

The collaboration with the Broad Institute and Whitehead Institute will evaluate a genome-wide CRISPR library against a panel of cancer cell lines with a view to identifying new targets for cancer drug discovery.

Whitehead Institute is a nonprofit research institution dedicated to improving human health through basic biomedical research. Wholly independent in its governance, finances and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments.

In addition to the new collaborations, AZ’s in-house program currently is adapting CRISPR technology to streamline and accelerate the production of cell lines and translational models that mimic complex genomic and disease-relevant scenarios.

“Application of the CRISPR technology for precise genome editing in recombinant cell lines and in relevant disease models should enable us to identify novel targets, build better test systems for drug discovery and enhance the translatability of our efficacy and safety models,” said Dr. Lorenz Mayr, vice president, reagents and assay development, AZ.

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