Synthetic small inhibiting RNAs: Efficient tools to inactivate oncogenic mutations and restore p53 pathways
- 28 October 2002
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 99 (23), 14849-14854
- https://doi.org/10.1073/pnas.222406899
Abstract
Single base pair mutations that alter the function of tumor suppressor genes and oncogenes occur frequently during oncogenesis. The guardian of the genome, p53, is inactivated by point mutation in more than 50% of human cancers. Synthetic small inhibiting RNAs (siRNAs) can suppress gene expression in mammalian cells, although their degree of selectivity might be compromised by an amplification mechanism. Here, we demonstrate that a single base difference in siRNAs discriminates between mutant and WT p53 in cells expressing both forms, resulting in the restoration of WT protein function. Therefore, siRNAs may be used to suppress expression of point-mutated genes and provide the basis for selective and personalized antitumor therapy.Keywords
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