LONDON—AstraZeneca has inked four new research collaborations, all of which center around CRISPR (clustered regularly interspaced short palindromic repeats) technology. This genome-editing technique enables scientists to alter specific genes more rapidly and precisely than ever before, and will allow AstraZeneca to identify and validate new drug targets in preclinical models of human disease. The company will share cell lines and compounds with its partners and collaborate with them to publish findings of its use of CRISPR technology.
“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,” Dr. Mene Pangalos, executive vice president of Innovative Medicines & Early Development at AstraZeneca, said in a press release. “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.”
The first of AstraZeneca's collaborations is with the Wellcome Trust Sanger Institute. Under the agreement, the organizations will research the potential of deleting specific genes linked to cancer, cardiovascular, metabolic, respiratory, autoimmune and inflammatory diseases and regenerative medicine to better understand the roles they play in those diseases. AstraZeneca will provide cells lines that can be targeted by the Sanger Institute’s genome-wide CRISPR guide-RNA libraries to create cell populations in which certain genes are switched off. Genes will then be identified by next-generation sequencing and cell populations tested to determine the effects of certain genes on different traits.
AstraZeneca will also collaborate with The Innovative Genomics Initiative, a joint venture between the University of California, Berkeley and University of California, San Francisco, to investigate the potential of inhibiting (CRISPRi) or activating (CRISPRa) genes to understand their role in disease pathology, specifically within cancer, cardiovascular, metabolic, respiratory, autoimmune and inflammatory diseases and regenerative medicine.
Thermo Fisher Scientific will be another collaborative partner, as it will provide AstraZeneca with RNA-guide libraries that target individual known human genes and gene families, which AstraZeneca can screen against cell lines to identify new disease targets.
The fourth collaboration is with the Broad Institute and Whitehead Institute, in which the organizations will evaluate a genome-wide CRISPR library against a panel of cancer cells lines in hopes of finding new targets for cancer drug discovery.
AstraZeneca is advancing its work with CRISPR technology on its own as well, as the company's in-house program is adapting the technology to streamline and accelerate production of cell lines and translational models that can mimic 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,” commented Dr. Lorenz Mayr, vice president of Reagents & Assay Development for AstraZeneca.
CRISPR technology features two components: a homing device to a specific piece of DNA (guide-RNA) and enzymatic 'scissors' that can cut DNA (Cas9 nuclease). In the nucleus, the guide-RNA sequence directs the Cas9 nuclease to cause double-stranded breaks in the target DNA sequence; then, by harnessing cells' natural DNA repair mechanisms, the gene target can be altered by deletion, adding nucleotides or turning its activity on or off.
SOURCE: AstraZeneca press release