GENERATION OF T7 RNA POLYMERASE TRANSGENIC MOUSE STRAIN

Utilizing the full scientific potential of the completed and on-going genome projects will require advances in technologies used to create research tools for functional genomics. Advances in the systems and techniques to create monoclonal antibodies in particular will be crucial importance, due to the critical role thee molecules play in unraveling protein function and their potential as novel human therapeutics. In this proposal, we plan to create a new system to derived monoclonal antibodies, which is both streamlined in development time and costs and is designed for high-throughput antibody production. Specifically, we plan to create a transgenic mouse, which expresses a cytoplasmic RNA polymerase, and use this mouse in immunizations with array-produced linear antigen gene templates. This system will eliminate the need for tedious and uncertain exogenous antigen protein production and allow simultaneous development and screening of multiple potential therapeutically or diagnostically relevant antibodies. In Phase One of this proposal, we shall create the transgenic mouse, develop the technology to produce, in array format, the linear antigen genes, and demonstrate the feasibility of this system to produce antibodies with a limited well- characterized set of these antigen genes. In Phase II, we shall use full arrays of antigen genes in these mice to demonstrate how this system can be used to screen for functional properties of multiple antibodies simultaneously. PROPOSED COMMERCIAL APPLICATIONS: The T7RNAP mouse will be a great tool for testing cDNAs for gene therapy and source of splenocytes for hybridoma production. The transgenic mice would be needed by scientists involved in gene therapy research and monoclonal antibody production. This mouse may be licensed to pharmaceutical companies involve din gene therapy to generate revenues from royalties. We thing this mouse would have great commercial value.