Restore Wild-Type Functions to P53 Mutants Using an RNA-Based Combinatorial Approach
Annual rept. 15 May 1998-14 May 1999
SRI INTERNATIONAL MENLO PARK CA
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Normal p53 protein is a transcription factor and a suppressor regulating the expression of a wide range of genes involved in apoptosis, growth control, and inhibiting the proliferation of tumor cells in animal models. Mutations that inactivate the p53 gene are important steps in tumor progression. The purpose of this project is to use combinatorial methods to select. RNA oligomers that will bind to the critical portion of mutant p53 protein to restore its ability to bind to specific DNA targets that allow it to act as a transcription factor. Such an RNA species could mimic the ability of antibodies directed against the same portion of p53 protein to restore wild-type function to mutants. Such RNAs could be expressed from viral vectors that could infect tumor cells and restore normal p53 functions, resulting in apoptosis. A critical region of the p53 peptide sequence has been chosen as the target for the selection of binding RNA oligomers. Five rounds of selection have been completed.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research