title: Interfering nanoparticles for silencing microRNAs.
abstract: MicroRNAs (miRNAs) are single-stranded noncoding RNAs ∼21-nucleotide (nt) in length and regulate gene expression at the posttranscriptional level. miRNAs are involved in almost every area of biology, including developmental processes, disease pathogenesis, and host-pathogen interactions. Dysregulation of miRNAs in various disease states makes them potential targets for therapeutic intervention. Specific miRNAs can be silenced by anti-microRNAs (anti-miRs) that are chemically modified antisense oligonucleotides complementary to mature miRNA sequences. In vivo delivery of anti-miRs is the main barrier in achieving efficient silencing of target miRNAs. A new systemic delivery agent, interfering nanoparticles (iNOPs), was designed and prepared from lipid-functionalized poly-L-lysine dendrimer. iNOPs can efficiently deliver small RNAs, including short interfering RNAs, miRNA mimics, and anti-miRs. Systemic delivery of a chemically stabilized anti-miR-122 by iNOPs effectively silences miR-122 in mouse liver. Intravenous administration of 2 mg/kg anti-miR-122 complexed with iNOP-7 results in 83% specific silencing of target miRNA. The specific silencing of miR-122 by iNOP-7 is long lasting and does not induce an immune response.
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
authors.forename: Huricha
authors.initials: H
authors.lastname: Baigude
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D008099:Liver / Q000378:metabolism; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D053769:Nanocapsules; D011107:Polylysine / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D050091:Dendrimers; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D053769:Nanocapsules; D034741:RNA, Small Interfering; D011107:Polylysine; D049410:Luciferases, Renilla