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

Autor: Gvozdeva OV; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia., Dovydenko IS; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia., Venyaminova AG; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia., Zenkova MA; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia., Vlassov VV; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia., Chernolovskaya EL; Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk 630090, Russia. Electronic address: elena_ch@niboch.nsc.ru.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2014 Mar 18; Vol. 588 (6), pp. 1037-43. Date of Electronic Publication: 2014 Feb 20.
DOI: 10.1016/j.febslet.2014.02.015
Abstrakt: 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.
(Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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