title: Silencing microRNA by interfering nanoparticles in mice.
abstract: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate post-transcriptional gene expression and are important in many biological processes. Disease-associated miRNAs have been shown to become potential targets for therapeutic intervention. Functions of miRNAs can be inhibited by using antisense oligonucleotides, called anti-miRs, complimentary to the miRNA sequences. Here, we show that systemic delivery of a chemically stabilized anti-miR-122 complexed with interfering nanoparticles (iNOPs) effectively silences the liver-expressed miR-122 in mice. Intravenous administration of 2 mg kg(-1) chemically modified anti-miR-122 complexed with iNOP-7 resulted in 83.2 ± 3.2% specific silencing of miR-122, which was accompanied by regulating gene expression in liver and lowering of plasma cholesterol. The specific silencing of miR-122 was long lasting and did not induce an immune response. Our results demonstrate that iNOPs can successfully deliver anti-miR to specifically target and silence miRNA in clinically acceptable and therapeutically affordable doses.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.forename: Huricha
authors.initials: H
authors.lastname: Baigude
authors.forename: Joshua
authors.initials: J
authors.lastname: McCarroll
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D000818:Animals; D002460:Cell Line; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D034622:RNA Interference
chemical_list: D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D016376:Oligonucleotides, Antisense