GlaxoSmithKline taps UC’s CRISPR expertise to speed drug discovery

Jennifer Doudna and Jonathan Weissman are the key players in a new collaboration with GlaxoSmithKline to apply CRISPR techniques to the discovery of new drug targets, potentially leading to new therapies for genetic diseases. (Barbara Ries photo courtesy of UCSF)

The pharmaceutical company GlaxoSmithKline ( GSK ) today announced a five-year collaboration with UC Berkeley and UCSF to establish a laboratory where state-of-the-art CRISPR techniques will be used to explore how gene mutations cause disease, potentially yielding new technologies using CRISPR that would rapidly accelerate the discovery of new medicines.

The new Laboratory for Genomics Research (LGR) is the brainchild of Jennifer Doudna, a co-inventor of CRISPR technology, UC Berkeley professor of molecular and cell biology and of chemistry and Howard Hughes Medical Institute investigator; Jonathan Weissman, a UCSF pioneer of CRISPR screening technology and an HHMI investigator; and Hal Barron, the Chief Scientific Officer and President for R&D at GSK.

With the recent explosion of information from human genetics, scientists need powerful tools to understand why small changes in a person’s genetic makeup can increase the risk of diseases, an area of science called functional genomics. The most powerful tool in functional genomics, CRISPR, allows this to be done at a scale once thought impossible. Through this research, scientists can discover and develop novel therapies that have a higher likelihood of becoming medicines.

"Technology is key to our innovation strategy at GSK, and CRISPR is one of the most important technologies of our time," Barron said. "With the expertise of Jennifer and Jonathan helping to steer the LGR, the mission of the lab is to advance our scientific understanding of the relationship between genes and disease to help find better medicines faster."

The LGR represents a novel hybrid model that brings together industrial and academic researchers under a single roof working on projects both together and independently. The outputs of those research projects will be focused on technologies, new drug targets and biological mechanisms that will foster both academic and industrial advances.

The new laboratory will also be a resource for investigators at both UC campuses, who will be able to access and use its technology to answer their own biomedical or other biological questions, and to develop new tools that explore how genes work.

"Over the last seven years, CRISPR has transformed academic research, but until the LGR, we haven’t had a focused effort to catalyze the kind of research we know will lead to new innovation using this CRISPR tool," said Doudna. "LGR is about building that space where creative science is partnered with the development of robust technology that will help develop tomorrow’s drugs. I think we’re going to be able to do science that none of us can even imagine today."

The LGR will receive up to $67 million over a five-year period, which will include funds to build facilities for 24 full-time university employees plus up to 14 full-time GSK employees. With a focus on immunology, oncology and neuroscience, the laboratory will be based near the UCSF Mission Bay campus in San Francisco.

GSK’s artificial intelligence and machine learning group will also be involved in building the necessary computational pipelines to analyze all the data. The LGR aims to automate and scale up existing CRISPR approaches. The ultimate goal is to deepen understanding of genetics and discover new targets, and to create next-generation technologies that will become future standard practice in the pharmaceutical industry.

"One of our key goals is to advance the field overall and make these tools as broadly available as possible," Weissman said. "The LGR screening center will enable labs at UCSF and Berkeley. Having access to it will give our scientists opportunities to advance their research in ways that would be very hard for them to do in their own labs."

In keeping with UC’s public mission, the tools that are developed in the lab will be described in published papers, subject to intellectual property provisions, and will be available for use by other academic and non-profit labs.

The collaboration will be governed by a joint steering committee with equitable UC and GSK representation, with additional joint sub-committees covering patents, scientific and project management. Doudna and Weissman will be members of the steering committee, together with GSK’s new head of functional genomics, Chris Miller, who just joined GSK from AbbVie. This builds on the work of the Innovative Genomics Institute - a separate UC Berkeley/UCSF nonprofit research center co-directed by Doudna and Weissman - whose mission is to use CRISPR to improve public health.

The collaboration will build on GSK’s existing collaborations with companies such as 23andMe, which delivers genetic information at scale. By applying artificial intelligence and machine learning to identify correlations between genetic variants and disease, researchers can select for clinical trials those patients who are most likely to benefit, thereby speeding up the drug development process.

The CRISPR-Cas9 system, invented in 2012 by Doudna and colleague Emmanuelle Charpentier, now a director of the Max Planck Institute for Infection Biology in Berlin, makes precise cuts in an organism’s DNA. The cell repairs such breaks through a sloppy approach that scrambles the DNA sequence or by patching the break with a new piece of DNA provided by the researcher. This enables scientists to keep a harmful gene from working or to add a helpful genetic sequence.