title: Silencing activity of 2'-O-methyl modified anti-MDR1 siRNAs with mismatches in the central part of the duplexes.
abstract: The thermodynamic properties of siRNA duplexes are important for their silencing activity. siRNAs with high thermodynamic stability of both the central part of the duplex and in the whole, usually display low silencing activity. Destabilization of the central part of the siRNA duplex could increase its silencing activity. However, mismatches located in the central part of the duplex could substantially decrease the amount of RNAi efficacy, hindering active RISC formation and function. In this study, we examined the impact of duplex destabilization by nucleotide substitutions in the central part (7-10 nt counting from the 5'-end of the antisense strand) of the nuclease-resistant siRNA on its silencing activity.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Petrova
authors.forename: Mariya I
authors.initials: MI
authors.lastname: Meschaninova
authors.forename: Alya G
authors.initials: AG
authors.lastname: Venyaminova
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.forename: Elena L
authors.initials: EL
authors.lastname: Chernolovskaya
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D020137:Base Pair Mismatch; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D009711:Nucleotides / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009711:Nucleotides; D034741:RNA, Small Interfering