AstraZeneca deals take CRISPR to its drug discovery heart

AstraZeneca has leveraged its "open-innovation" approach to strike four deals in the ground-breaking CRISPR genome editing field, positioning it well against its pharma peers.

Experts say CRISPR is set to change the way biomedical research is conducted. The technology has the potential to reduce attrition rates by improving cell lines/transgenic animal models, boosting the quality of drug candidates and the speed with which they are produced, and even possibly reducing the size of clinical trials further down the line.

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 has been possible with other techniques, such as zinc-finger nucleases. It is also said to be easier to handle in the laboratory.

Naturally, since its invention, big pharma has been keen to get in on the act, with some companies (including AstraZeneca) developing their own in-house CRISPR efforts as well as looking to partner with biotech start-ups. Earlier this month, Novartis announced agreements with Intellia Therapeutics and Caribou Biosciences using the CRISPR technology (scripintelligence.com, 7 January 2015). And in December, another pioneer company Editas Medicine signed several license agreements with universities for intellectual property underlying its CRISPR platforms (scripintelligence.com, 5 December 2014).

AstraZeneca (amid excitement about the technology at its highest echelons) has teamed up with three well-known academic partners – the UK's Wellcome Trust Sanger Institute, the Innovative Genomics Initiative in California, and the Broad Institute/Whitehead Institute in Cambridge, Massachusetts. Its fourth partnership is with the reagent and instrument provider Thermo Fisher Scientific.

While none of the parties involved will own the targets identified, the collaborations will allow AstraZeneca to use genome-editing technique across its entire discovery platform in the company's key therapeutic areas (oncology, inflammation/immunology and cardiovascular/metabolic), helping it validate new drug targets in preclinical models that closely resemble human disease. This makes the deals less niche than would perhaps be the case with partnering with start-up biotechs.

The deals' announcement is the culmination of a strategic approach by the firm to team up with the "best people in academia" and to be free with the fruits of the combined CRISPR research. AstraZeneca will share cell lines and compounds with its partners and work with them to publish the findings of its application of CRISPR technology in peer-reviewed journals. Dr Lorenz Mayr, the company's vice president of reagents & assay development, told Scrip this commitment to open innovation was what chiefly attracted its partners in choosing to team up with AstraZeneca in this highly competitive and fast-moving field. While the deals are not exclusive, he noted that it would be difficult for the academics involved to partner as effectively with AstraZeneca's rivals.

Deal details

• The Wellcome Trust Sanger Institute collaboration will focus on deleting specific genes involved in cancer, cardiovascular, metabolic, respiratory, autoimmune & inflammatory diseases and regenerative medicine to understand their precise role. 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.
• The Innovative Genomics Initiative (IGI) collaboration will focus on either inhibiting (CRISPRi) or activating (CRISPRa) genes to understand their role in disease pathology. The IGI and AstraZeneca will work 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.
• The Broad Institute/Whitehead Institute collaboration 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.
• The Thermo Fisher Scientific collaboration will provide AstraZeneca with 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.
• Financial details were not disclosed.