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Vol 44(2010) N 2 p. 254-261;
N.S. Kruglova, M.I. Meschaninova, A.G. Ven'yaminova, M.A. Zenkova, V.V. Vlasov, E.L. Chernolovskaya*

Cholesterol-Modified Anti-MDR1 Small Interfering RNA: Uptake And Biological Activity

Institute of Chemical biology and Fundamental Medicine of Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090 Russia

*elena_ch@niboch.nsc.ru
Received - 2009-07-01; Accepted - 2009-07-23

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 transfectant reagent, the levels of both carrier-free and chol-siRNAs were very low, whereas transfectant reagent 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.

siRNA, multiple drug resistance, cholesterol, 2'-O-methyl-ribonucleotides



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