title: Silencing of Inducible Immunoproteasome Subunit Expression by Chemically Modified siRNA and shRNA.
abstract: Overexpression of inducible subunits of immunoproteasome is related to pathogenesis of some chronic diseases. Specific inhibition of the immunosubunits may be used for the treatment of these diseases and RNA interference is one of the potent methods used in this area. We designed 2'-O-methyl modified siRNAs with selectively protected nuclease-sensitive sites, which efficiently silence LMP2, LMP7, and MECL-1 genes expression. To provide stable long-lasting inhibition of target genes, short-hairpin RNAs (shRNA) expressed by lentiviral vectors were constructed. Our results demonstrated that chemically modified siRNAs inhibited the expression of target genes with similar efficiency or with efficiency exceeding that of corresponding shRNAs and provide silencing effect for 5 days.
authors.affiliation: a Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk , Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Gvozdeva
authors.affiliation: b Engelhardt Institute of Molecular Biology RAS , Moscow , Russia.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Prassolov
authors.affiliation: a Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk , Russia.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
authors.affiliation: a Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk , Russia.
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.affiliation: a Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk , Russia.
authors.forename: Elena L
authors.initials: EL
authors.lastname: Chernolovskaya
mesh_terms: D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D003562:Cytidine / Q000031:analogs & derivatives / Q000737:chemistry; D015870:Gene Expression; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering; C071313:LMP-2 protein; C052202:2'-O-methyluridine; C052203:2'-O-methylcytidine; D003562:Cytidine; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; D014529:Uridine
keywords: chemical modifications; immunoproteasome; lentiviruses; shRNA; siRNA