42‐ and 63‐bp anti‐MDR1‐siRNAs bearing 2′‐OMe modifications in nuclease‐sensitive sites induce specific and potent gene silencing. Issue 6 (20th February 2014)

• Record Type: Journal Article
• Authors: Gvozdeva, Olga V.; Dovydenko, IIya S.; Venyaminova, Alya G.; Zenkova, Marina A.; Vlassov, Valentin V.; Chernolovskaya, Elena L.
• Is Part Of: FEBS letters. Volume 588:Issue 6(2014)
• Page Start: 1037
• Page End: 1043
• Publication Date: 2014-02-20
• Subjects: 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 -- small interfering RNA -- Dicer-substrate RNAs -- Interferon response -- 2′-O-methyl modification; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.02.015
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : We design selectively 2′‐O‐methyl modified 42 and 63bp anti‐MDR1‐siRNAs. We examine their ability to silence the expression of the target gene and the specificity of their action. We show that 42 and 63bp siRNAs induce more effective RNAi at lower concentrations than classical 21bp siRNA. These siRNAs act in a Dicer‐independent mode and are devoid of immunostimulating properties.