The focus of the collaboration is to apply rAAV gene targeting in mouse embryonic stem (ES) cells, and for the discovery of genes involved in resistance to EGFR-targeted therapies in human cancer, such as PI3K.
The collaboration will generate new human isogenic disease models and mouse knock-out models that will be exclusively licensed by Fox Chase to Horizon in return for future product royalties. Horizon will also have an exclusive option to license new intellectual property developed during the term of the collaboration. This forms part of Horizon’s strategy to generate at least 2500 new X-MANTM (gene X- Mutant And Normal) models of cancer, neurodegenerative, and cardiovascular disease. These models will support drug discovery researchers in their effort to understand how complex genetic diseases manifest themselves in real patients and help rationalize many aspects of drug development, reducing the cost of bringing to market new personalized therapies.
As part of the collaboration, Horizon and Fox Chase will establish a Center of Excellence in gene editing that will advance the application of rAAV gene-editing in functional genomics and translational medicine within in vivo mouse models, further extending the range of applications and models within the GENESIS Gene Editing Consortium. In December 2010, Horizon announced that it plans to 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 modeling of genetic diseases in human cells in vitro.
Dr Rob Howes, Principal Scientist and Center of Excellence Program Manager at Horizon, said: “EGFR-targeted therapies, such as Erbitux and Vectibix, have been very effective in treating human cancers but there is a set of patients which are resistant to these treatments. Our collaboration with Fox Chase will identify genes which are involved in this resistance mechanism and provide novel targets for cancer treatment. The ability of rAAV to edit the genome of human cells is now routine. Establishing the rAAV Center of Excellence at Fox Chase will enable us to extend the applicability of rAAV to mouse gene targeting.”
Dr Jonathan Chernoff, Chief Scientific Officer at Fox Chase, commented: “These efforts will allow us to more realistically model how combining new signaling inhibitors affects certain drug-resistant cancers. In addition, if we are able to use rAAV technology to modify mouse ES cells, this could open the door to rapid, high throughput gene editing in the mouse.”