Cambridge Enterprise company in collaboration with the National Cancer Institute and the National Human Genome Research Institute

Cambridge Enterprise portfolio company Horizon Discovery (Horizon), a leading provider of research tools to support the development of personalised medicines, has entered into a three year Technology Access Agreement with the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both divisions of the National Institutes of Health, the USA’s medical research agency.

The focus of the agreement is to enable the NCI and NHGRI to apply Horizon’s rAAV gene editing technology (GENESIS™) to engineer human isogenic disease models for its researchers. The project aims to generate 10s of new X-MAN™ (gene X- Mutant and Normal) cell lines annually, to advance both basic research and translational medicine. The initial set of 18 projects from eight laboratories will focus on developing disease models for melanoma, prostate, colon and kidney cancer, genes involved with chromatin and chromosome function, and cell lines complementary to existing mouse cancer disease models.

The new human isogenic disease models generated under the agreement may have utility for future cancer studies. This agreement forms part of Horizon’s strategy to foster development of at least 2,500 new X-MAN models of cancer, neurodegenerative & cardiovascular disease. These models will support drug discovery researchers in understanding how complex genetic diseases manifest themselves in patients, and reduce the cost of bringing to market new personalised therapies by helping to streamline many aspects of drug development.

As part of the agreement, the NCI will serve as a Center of Excellence in gene editing, with a core research group to provide disease models for the 256 investigators at the NCI. Horizon will also work directly with the NHGRI to develop isogenic disease models for melanoma. This will advance the application of rAAV gene-editing, further extending the range of applications within the GENESIS Gene Editing Consortium. In December 2010, Horizon announced that it will commit resources to provide training and open access to its proprietary gene-editing platform to another 50 academic and not-for-profit research groups over the next five years.

At the heart of the GENESIS platform is the use of rAAV vectors that have a unique and powerful property in performing accurate and efficient gene-editing functions in human cells by switching on a natural and high-fidelity DNA-repair mechanism called homologous recombination (HR). When harnessed using rAAV gene-editing vectors, HR allows the precise alteration of any DNA sequence, permitting the correction of genetic defects in gene therapy applications, or the accurate modelling of genetic diseases in human cells in vitro.

Dr Rob Howes, Principal Scientist and Center of Excellence Program Manager at Horizon, said: “The establishment of a Center of Excellence at the NCI/NHGRI is a fundamental pillar in our strategy for this program. By bringing together the quality and breadth of research at the NCI/NHGRI with Horizon’s GENESIS technology we will develop disease models that will underpin the research at the NCI and NHGRI. These models will have applications in basic research and throughout the drug discovery process, with the ultimate aim of improving patient survival by producing better targeted therapies.”

Dr Darrin M Disley, CEO of Horizon said: “We are delighted to be able to enter into this agreement with the NCI/NHGRI as it is one of our core missions to support the unlocking of the human genome project for the benefit of all. Our rAAV gene-editing platform will enable NCI/NHGRI scientists to speed up key research in translational genomics and the development of personalised cancer medicines.”