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

Authors :: Gvozdeva OV
Dovydenko IS
Venyaminova AG
Zenkova MA
Vlassov VV
Chernolovskaya EL
Source :: FEBS letters [FEBS Lett] 2014 Mar 18; Vol. 588 (6), pp. 1037-43. Date of Electronic Publication: 2014 Feb 20.
Publication Year :: 2014
Abstract: DsRNAs longer than 30bp induce interferon response and global changes in gene expression profile in mammalians. 21bp siRNA and 25/27bp 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 63bp 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 21bp siRNAs. We also show that they act in a Dicer-independent mode and are devoid of immunostimulating properties. Our findings suggest that 42 and 63bp siRNAs could be used as potential therapeutics.<br /> (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Subjects :: ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism
Antineoplastic Agents, Phytogenic pharmacology
Cell Line, Tumor
Cell Survival drug effects
Gene Expression
Gene Knockdown Techniques
Humans
RNA Processing, Post-Transcriptional
RNA, Small Interfering chemistry
RNA, Small Interfering metabolism
Ribose analogs & derivatives
Ribose chemistry
Vinblastine pharmacology
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Drug Resistance, Neoplasm
RNA Interference
RNA, Small Interfering genetics

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