AstraZeneca entered into four research collaborations looking to tap into the power of CRISPR gene-editing technology. Company officials say the technique will allow AstraZeneca to identify and validate new drug targets in preclinical models that closely resemble human disease. The firm, which already has an in-house CRISPR program, 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.

One collaboration is with The Wellcome Trust Sanger Institute, and it 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. AstraZeneca 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.

Another agreement with the Innovative Genomics Initiative (IGI) zeroes in on either inhibiting (CRISPRi) or activating (CRISPRa) genes to understand their role in disease pathology. IGI and AstraZeneca will seek 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 a deal with Thermo Fisher Scientific AstraZeneca  receives RNA-guide libraries that target individual known human genes and gene families. AstraZeneca can screen these guides against cell lines to identify new disease targets.

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

“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. By combining the great science from our labs with these world-renowned academic and industry partners, we will be able to integrate this ground-breaking technology into our research  and help accelerate the discovery of novel treatments for patients,” said  Mene Pangalos, Ph.D., executive vp, innovative medicines and early development, at AstraZeneca.

“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,” added Lorenz Mayr, Ph.D., AstraZeneca’s vp of reagents and assay development.

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