In vivo inhibition by a site-specific catalytic RNA subunit of RNase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment.

摘要: One major obstacle to the effective treatment of cancer is distinguish between tumor cells and normal cells. The chimeric molecules created by cancer-associated chromosomal abnormalities are ideal therapeutic targets because they unique disease. We describe use a novel approach based on catalytic RNA subunit RNase P destroy specifically tumor-specific fusion genes as result chromosome abnormalities. Using target model abnormal BCR-ABL p190 p210 products, we constructed M1-RNA with guide sequences that recognized oncogenic messengers at point (M1-p190-GS M1-p210-GS). To test effectiveness specificity M1-p190-GS M1-p210-GS, studied in vitro vivo effects these enzymes againstBCR-ABLp190 andBCR-ABLp210, bearing mind both share ABL sequence but differ coming from BCR gene. showed M1-p210-GS can act sequence-specific endonucleases exclusively cleave forms base pair (GS). also demonstrated when were expressed proper mammalian cell models, abolished effect decreasing amount mRNA preventing function theBCR-ABL oncogenes. These data clearly demonstrate usefulness activity M1-GS human represent treatment.