期刊
MOLECULAR BIOLOGY
卷 44, 期 2, 页码 254-261出版社
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1134/S002689331002010X
关键词
siRNA; multiple drug resistance; cholesterol; 2 '-O-methyl-ribonucleotides
资金
- Russian Academy of Sciences [02.512.11.2200]
- Russian Foundation for Basic Research [08-04-01073]
- Siberian Branch of the Russian Academy of Sciences [41]
Small interfering RNAs (siRNA) are considered to be potential agents for specific gene silencing, but low the efficacy of siRNA delivery into cells limits their biomedical application. Accumulation of siRNA coupled with cholesterol residue at the 5'-end of the sense strand (chol-siRNA) was studied in HEK293, HepG2, SC1, and KB-8-5 cells. In the absence of a transfection agent, the levels of both carrier-free and chol-siRNAs were very low, whereas transfection agent substantially increased transfection rate in all cell lines; in HEK293, SC1, and KB-8-5 cells transfection efficiency of the chol-siRNA was higher than that of the corresponding unmodified siRNA. Biological activity of anti-MDR1-siRNAs targeted to the 557-577 nt region of the MDR1 gene mRNA was estimated as multiple drug resistance phenotype reverting activity of KB-8-5 cancer cells. The chol-siRNA induced cancer cells' death in the presence of previously tolerated vinblastine doses more effectively than unmodified siRNA.
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