Thursday, 29 January 2015
AstraZeneca today 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 technology will allow AstraZeneca to identify and validate new drug targets in preclinical models that closely resemble human disease. AstraZeneca 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 AstraZeneca’s in-house CRISPR programme and will build on the company’s ‘open innovation’ approach to research and development.
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 & Early Development, AstraZeneca, 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. 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.”
AstraZeneca’s research collaborations are with the following institutions:
The Wellcome Trust Sanger Institute, Cambridge, UK
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 & 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.
“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 behaviour 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, California
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 AstraZeneca 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.
“We are excited to pair the IGI’s premier expertise in CRISPR gene editing and regulation with AstraZeneca’s deep experience in therapeutics,” said Jacob Corn, Scientific Director of the Innovative Genomics Initiative. “I’m confident that, working side-by-side with scientists at AstraZeneca, our collaboration will positively impact drug discovery and development to hasten treatments to patients.”
Thermo Fisher Scientific, Waltham, Massachusetts
Under the terms of the collaboration with Thermo Fisher Scientific, a world-leading reagent and instrument provider, AstraZeneca will receive 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.
“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.
Broad Institute/Whitehead Institute, Cambridge, Massachusetts
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.
In addition to the new collaborations, AstraZeneca’s in-house programme is currently 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 & Assay Development, AstraZeneca.
The short video above explaining how CRISPR technology works is available in English, Mandarin and Spanish, and a still image illustrating the technology is available.
About The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk/
About Innovative Genomics Initiative
The Innovative Genomics Initiative (IGI) was established in early 2014 at the Li Ka Shing Center for Genomic Engineering at the University of California, Berkeley, and is a joint UC Berkeley/UC San Francisco initiative catalyzing and guiding the global effort in both the academic and commercial research communities to unleash the transformative potential of CRISPR/Cas9 technology for positive human impact.
About the Broad Institute of Harvard and MIT
The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.
Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.
About Whitehead Institute
Whitehead Institute is a world-renowned non-profit 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. http://wi.mit.edu
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. is the world leader in serving science, with revenues of $17 billion and 50,000 employees in 50 countries. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics and increase laboratory productivity. Through our four premier brands – Thermo Scientific, Life Technologies, Fisher Scientific and Unity Lab Services – we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive support. For more information, please visit www.thermofisher.com.
NOTES FOR EDITORS
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
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