42- and 63-bp anti-MDR1-siRNAs bearing 2′-OMe modifications in nuclease-sensitive sites induce specific and potent gene silencing |
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Authors: | Olga V. Gvozdeva IIya S. DovydenkoAlya G. Venyaminova Marina A. ZenkovaValentin V. Vlassov Elena L. Chernolovskaya |
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Affiliation: | Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia |
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Abstract: | DsRNAs longer than 30 bp induce interferon response and global changes in gene expression profile in mammalians. 21 bp siRNA and 25/27 bp dsiRNA acting via RNA interference mechanism are used for specific gene silencing in this class of organisms. We designed selectively 2′-O-methyl-modified 42 and 63 bp anti-MDR1-siRNAs that silence the expression of P-glycoprotein and restore the sensitivity of drug-resistant cancer cells to cytostatic more efficiently than canonical 21 bp siRNAs. We also show that they act in a Dicer-independent mode and are devoid of immunostimulating properties. Our findings suggest that 42 and 63 bp siRNAs could be used as potential therapeutics. |
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Keywords: | RNAi, RNA interference siRNA, small interfering RNA MDR, multiple drug resistance FBS, fetal bovine serum MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide IFN, interferon |
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