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AstraZeneca and Cancer Research UK launch joint Functional Genomics Centre in Cambridge




Dr Mene Pangalos, executive vice president, IMED Biotech Unit and Global Business Development, AstraZeneca. Picture: AstraZeneca / Marcus Lyon (5876664)
Dr Mene Pangalos, executive vice president, IMED Biotech Unit and Global Business Development, AstraZeneca. Picture: AstraZeneca / Marcus Lyon (5876664)

AstraZeneca and Cancer Research UK have today (December 10) announced a multi-million pound collaboration in Cambridge that will drive forward new medicines and deepen our understanding of the biology of cancer.

The Functional Genomics Centre will be located within the University of Cambridge’s Milner Therapeutics Institute on Cambridge Biomedical Campus.

It aims to be a centre of excellence in genetic screening, cancer modelling and big data processing, and will deploy CRISPR technology to create new biological models more reflective of human disease.

Dr Mene Pangalos, executive vice president of Innovative Medicines & Early Development (IMED) at AstraZeneca, explained in an advanced briefing to the Cambridge Independent that the centre represents the latest stage in the biopharmaceutical company’s drive to push up the success rates of its drug programmes and is another tangible sign of the benefits it sees of collaborating in Cambridge.

“We’re constantly having to reinvent ourselves, evolve, improve and get better every year at what we do,” he said. “This collaboration is an attempt to maintain this leadership position relative to our peers in turning science into medicine.”

Greg Hannon, the director of CRUK Cambridge Institute. Picture: Keith Heppell
Greg Hannon, the director of CRUK Cambridge Institute. Picture: Keith Heppell

Greg Hannon, director of the CRUK Cambridge Institute, said: “The goal here is to form a centre that can drive innovation and make sure we stay at the cutting edge, but also importantly democratise that capability throughout the CRUK family.”

Functional genomics describes the complex relationship between genetic changes within our DNA and cellular changes in disease

Understanding the genetic drivers of disease can enable scientists to make better selections for drug targets, improving the chances of success in the clinic.

AstraZeneca has raised its success rate - measured by the proportion of molecules entering the pre-clinical setting that go on to be launched as new medicines - from just four per cent in the period of 2005-10 to 19 per cent in 2012-16, following a major cultural shift in its approach to research and development.

With the aid of new tools such as CRISPR, described at Friday’s briefing as “one of the most important scientific advances” of the last decade, the company believes it can do better still.

CRISPR technology for genome editing. Picture: AstraZeneca (5876662)
CRISPR technology for genome editing. Picture: AstraZeneca (5876662)

CRISPR, a gene-editing technology discovered in 2012, offers researchers the power to identify a specific DNA sequence, remove it, replace it or add to it.

AstraZeneca has also announced an extension of its collaboration, launched in 2015,with the Wellcome Sanger Institute at Hinxton, which gives the company access to the latest CRISPR libraries.

These libraries are a collection of reagents and guide RNAs (gRNAs) each designed to edit one specific part of the genome, and can be used to perform large screens with disease models. They can be used to silence or activate every gene in the genome.

Dr Sarah Teichmann, of Wellcome Sanger Institute. Picture: Pari Naderi
Dr Sarah Teichmann, of Wellcome Sanger Institute. Picture: Pari Naderi

Dr Sarah Teichmann, head of cellular genetics at the Wellcome Sanger Institute, said: “The key to these Sanger libraries is they are very large and very precise. What that allows is comprehensive, effective and sensitive screening.”

Dr Pangalos explained: “If you have a cancer cell that you want to show has a certain driver and you want to see a gene that kills it, with this type of screen, you can test every gene in the genome. You can look at which genes - when you switch them off, or downregulate their expression - kill that particularly cancer cell, and you can do it very, very rapidly.”

Ultan McDermott, chief scientist, oncology, in AstraZeneca’s IMED Biotech Unit, added: “If I turn a gene off and a cancer cell dies, that’s a new target. If you turn it on or off and a cancer cell no longer responds to a drug in the clinic, that’s resistance. Can we adapt to that in the clinic?”

The CRISPR libraries can also be used across AstraZeneca’s cardiovascular, metabolism renal and respiratory disease areas.

And they will benefit Cancer Research UK’s work too.

Dr Iain Foulkes, CRUK’s executive director of research and innovation, said: “We’re delighted to collaborate with AstraZeneca on this exciting new initiative, which will give leading Cancer Research UK scientists and our alliance partners access to the latest in CRISPR technology.

“As we move into an era of personalised medicine, we’ve reached a turning point in our ability to harness powerful technologies in the pursuit of targeted cancer therapies.

“We hope that this will translate into urgently needed new therapies for patients with hard-to-treat cancers such as lung, pancreatic, oesophageal and brain tumours.”

Research at AstraZeneca. Picture: Marco Betti / AstraZeneca (5876658)
Research at AstraZeneca. Picture: Marco Betti / AstraZeneca (5876658)

The Functional Genomics Centre will sit within the Milner Research Labs, part of the Milner Therapeutics Institute, set up with funding from biotech pioneer Jonathan Milner and the University of Cambridge to bring academia and industry closer together.

The labs will form part of the Cappella building on the biomedical campus, and are due to open in the first quarter of 2019.

Dr Tony Kouzarides, director of the Milner Therapeutics Institute, said: “What we try to do is break down the physical barriers of interaction between academia and industry by having staff working side-by-side. The Functional Genomics Centre is a great example of this.”

Under the collaboration - initially plotted as a five-year agreement, although there is every expectation that it could be renewed - both AstraZeneca and CRUK scientists will have independent use of the centre’s facilities, and their scientists will also work alongside one another to innovate and make scientific progress.

The Capella building will also house the Wellcome-MRC Cambridge Stem Cell Institute and the Cambridge Institute of Therapeutic Immunology and Infectious Diseases. It lies next to the CRUK Cambridge Institute, and a few minutes’ walk from where AstraZeneca is building its £500million-plus new global HQ and R&D centre, set to open in 2020.

How Cambridge Biomedical Campus will look (5876660)
How Cambridge Biomedical Campus will look (5876660)

Dr Pangalos told the Cambridge Independent: “This proximity is one of the things that makes Cambridge so attractive. It’s like being in the middle of Boston but we’re the only pharma company here. It’s really quite unique and a real opportunity and we couldn’t be happier about the move that we’ve made.”

The Functional Genomics Centre is funded 50-50 by AstraZeneca and CRUK, although the amount has not been disclosed. Preliminary research will begin in January, with lab work expected to begin July.

Dr Pangalos said: “The best science doesn’t happen in isolation, which is why AstraZeneca is committed to advancing innovative science through collaboration. This new centre of excellence with Cancer Research UK will combine our expertise in functional genomics and CRISPR technology to identify new biological pathways driving disease and will accelerate the development of new cancer medicines for patients.”

AstraZeneca scientists discuss a development compound. Picture: AstraZeneca (5876654)
AstraZeneca scientists discuss a development compound. Picture: AstraZeneca (5876654)

AstraZeneca also announced a separate collaboration with California-based Innovative Genomics Institute (IGI) focused on using CRISPR to uncover genes and disease pathway mechanisms involved in DNA damage response (DDR)

Representing IGI at Friday’s briefing, CRISPR pioneer Dr Luke Gilbert, an assistant professor at the University of California San Francisco, said: “Normal cells repair damage very efficiently. This is dysregulated in cancer biology.

“We want to know how this happens, what we can do about it and how we can target it therapeutically. My lab, in our collaboration with AstraZeneca, is using our CRISPR technologies to turn every gene in the genome on and off and asking how that contributes to DNA repair biology that is dysregulated in cancer and how can we target that therapeutically.”

The research will focus on identifying strategies for DDR inhibitors, including combinations, in oncology. It extends AstraZeneca’s previous collaboration with IGI, which is led by Prof Jennifer Doudna at the University of California Berkeley.

Read more from a round table with Mene Pangalos, Ultan McDermott, Steve Rees, Greg Hannon, Hamish Ryder, Sarah Teichmann, Tony Kouzarides and Luke Gilbert in the Cambridge Independent, available from Wednesday December 12.

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