Edinburgh seeks collaboration for “human-mouse” models

Collaboration / Licensing Opportunity

The University of Edinburgh is seeking commercial partners to evaluate and develop the applications of its transgenic technology.  The University is looking for out-licensing opportunities and would consider funded industrial collaboration.

Researchers have perfected a genetic engineering strategy in mouse embryonic stem cells to replace large regions of mouse chromosomal sequences (>100kb) with the corresponding human syntenic region.  This state-of-the-art embryonic stem cell genetic engineering has the potential to achieve "humanisation" of mice on an unprecedented scale for functional analysis and disease modelling.

“Fundamentally we would like to commercialise this technology by out-licensing to a suitable commercial party. I suspect “suitable” will be defined as a party with significant expertise in genetic engineering and one that most likely supplies bespoke animal models for research and drug development activities,” said Wendi Nicholson, business manager at Edinburgh Research and Innovation.

“The technology would be best licensed non-exclusively, however, we are not opposed to an exclusive deal if the opportunity arises,” Nicholson added, “We are not looking to set up a company ourselves to do this, nor are we looking to set up an in-house service. However, we would be open to sponsored research or service work if the project was suitably attractive to the research group involved in developing the technology.”

The research has been carried out in collaboration with an MRC unit at the University of Oxford, so the development of this technology is itself a result of collaboration.

The Recombinase Mediated Genomic Replacement technology combines aspects of various known technologies (gene targeting, Cre and FLP recombination) in a novel way such that it allows precise, reproducible and genetically selectable genomic replacement on a scale that will permit the generation of improved mouse models for studying human disease.

This method has been exemplified at the University of Oxford by generating a mouse that produces only the human globin chains. It has also generated an accurate model of the human disease thalassemia and is the subject of a recent Cell publication that describes the method in detail (Wallace et al., Cell 128, 197-209. 2007).

Key Benefits

• Genome replacement is precise and reproducible
• Genome replacement leaves no genetic selection markers in place
• Equivalent murine sequences are eliminated from the genome, therefore obviating any requirement to breed with knock-out lines
• An unlimited number of replacement events can be made with variously modified BAC sequences
• Germline-transmitting embryonic stem cells are established
• Genome replacement region can be made homozygous

Applications

• Mutational analysis of complex global regulatory regions by in-vitro differentiation of embryonic stem cells and/or in mice 
• In vivo single nucleotide polymorphism screening to identify quantitative trait loci, eg. for pharmacogenomic studies
• Humanisation of large gene clusters, eg. immunoglobulin genes and major histocompatibility complex genes, to produce more accurate mouse models

The technology has a priority UK patent application filed and is available for licensing.