TY - JOUR
T1 - Synthetic small inhibiting RNAs
T2 - Efficient tools to inactivate oncogenic mutations and restore p53 pathways
AU - Martinez, Luis Alfonso
AU - Naguibneva, Irina
AU - Lehrmann, Heike
AU - Vervisch, Arlette
AU - Tchénio, Thierry
AU - Lozano, Guillermina
AU - Harel-Bellan, Annick
PY - 2002/11/12
Y1 - 2002/11/12
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.222406899
DO - 10.1073/pnas.222406899
M3 - Article
C2 - 12403821
AN - SCOPUS:0037069330
SN - 0027-8424
VL - 99
SP - 14849
EP - 14854
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -