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42‐ and 63‐bp anti‐MDR1‐siRNAs bearing 2′‐OMe modifications in nuclease‐sensitive sites induce specific and potent gene silencing
Author(s) -
Gvozdeva Olga V.,
Dovydenko IIya S.,
Venyaminova Alya G.,
Zenkova Marina A.,
Vlassov Valentin V.,
Chernolovskaya Elena L.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.015
Subject(s) - nuclease , gene silencing , small interfering rna , gene , chemistry , microbiology and biotechnology , biology , genetics , rna , biochemistry
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.