42- and 63-bp anti-MDR1-siRNAs bearing 2鈥?OMe modifications in nuclease-sensitive sites induce specific and potent gene silencing

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• 作者：Olga V. Gvozdeva ; IIya S. Dovydenko ; Alya G. Venyaminova ; Marina A. Zenkova ; Valentin V. Vlassov ; Elena L. Chernolovskaya ; ^{elena_ch@niboch.nsc.ru" class="auth_mail}
• 关键词：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
• 刊名：FEBS Letters
• 出版年：18 March, 2014
• 年：2014
• 卷：588
• 期：6
• 页码：1037-1043
• 全文大小：1143 K

文摘

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鈥?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.