Inducible Mutagenesis of Target Genes

Introduction The B cell alters its genome during differentiation, and under environmental signals. The plasma cell DNA is rearranged during the cell’s development from a B cell to create the antibody-encoding genes. The genetic mechanisms contributing to variability are 1/ somatic hypermutation that inserts point mutation and 2/ gene conversion that inserts mutations
“templated” by related but non-identical sequences. Technology description Dr Nancy Maizels’ laboratory has developed a method that enables inducible mutagenesis in cells. Gene conversion is the mechanism of mutagenesis by default and methods to cause a polarization on hypermutation or gene conversion are provided. Additionally, this system can support simultaneous hypermutation of two targets, at both the lgH and Igl alleles. Alternatively, the invention is readily extended to promote mutagenesis at either the heavy and light chain genes or at both sequentially. Business Opportunity Antibodies are used as therapeutics in treatment of a variety of diseases from infectious diseases to cancer. They are also used as diagnostic reagents in a huge variety of tests carried out daily in clinical and research laboratories. Dr Maizels’ invention comprises a method for rapidly and inducibly generating point mutations in expressed antibody genes. This method can be coupled with selection to identify B cell clones which produce antibodies for high affinity or specificity. Intellectual Property Position The University of Washington has applied for patent protection to secure the rights to this technology. Related Publication(s)
PLoS Biology 2007 October; 5 (10): 2145-2155.

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