Pharmacother

Pharmacother

Pharmacother. and more difficult strategy of creating gene knockouts. Second of all, microRNA targeting represents a novel and still undeveloped approach toward potential therapeutic applications. Oligonucleotide (ON) analogs inhibit microRNA function essentially by a steric block, RNase H-independent and RISC-independent, antisense mechanism through complementary binding of the ON to the microRNA sequence. The cellular outcome of such binding is still unclear, with reports arguing either in favor of a mechanism based on simple sequestration by stoichiometric complex formation between the mature microRNA and the ON inhibitor (Chan et al. 2005), or in favor of a yet unknown mechanism by which complex formation leads to degradation of the target microRNA (Krutzfeldt et al. 2005, 2007; Esau et al. 2006). A number of ON analog PLX-4720 types have been proposed that provide both metabolic stability as well as good RNA binding, two fundamental requirements for microRNA inhibition. Early literature reports showed that well established 2-heterochromic gene lin-4 encodes small RNAs with antisense complementary to lin-14. Cell. 1993;75:843C854. [PubMed] [Google Scholar]Liu, J., Valencia-Sanchez, M.A., Hannon, G.J., Parker, R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 2005;7:719C723. [PMC free article] [PubMed] [Google Scholar]Meister, G., Landthaler, M., Dorsett, Y., Tuschl, T. Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA. 2004;10:544C550. [PMC free article] [PubMed] [Google Scholar]Moschos, S.A., Williams, A.E., Perry, M.M., Birrell, M.A., Belvisi, M.G., Lindsay, M.A. Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids. BMC Genomics. 2007;8:240. doi:?10.1186/1471-2164-8-240. [PMC free article] [PubMed] [CrossRef] [Google Scholar]Naguibneva, PLX-4720 I., Ameyar-Zazoua, M., Nonne, N., Polesskaya, A., Ait-Si-Ali, S., Groisman, R., Souidi, M., Pritchard, L.L., Harel-Bellan, A. An LNA-based loss-of-function assay for PLX-4720 micro-RNAs. Biomed. Pharmacother. 2006;60:633C638. [PubMed] [Google Scholar]Nielsen, P.E., Egholm, M., Buchardt, O. Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone. Bioconjug. Chem. 1994;5:3C7. [PubMed] [Google Scholar]O’Connell, R.M., Taganov, K.D., Boldin, M.P., Cheng, G., Baltimore, D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. Rabbit Polyclonal to MAP3K4 2007;104:1604C1609. [PMC free article] [PubMed] [Google Scholar]O’Donnell, K.A., Wentzel, E.A., Zeller, K.I., Dang, C.V., Mendell, J.T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839C843. [PubMed] [Google Scholar]?rom, U.A., Kauppinen, S., Lund, A.H. LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene. 2006;372:137C141. [PubMed] [Google Scholar]Richard, J.P., Melikov, K., Brooks, H., Prevot, P., Lebleu, B., Chernomordik, L.V. Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors. J. Biol. Chem. 2005;280:15300C15306. [PubMed] [Google Scholar]Roberts, J., Palma, E., Sazani, P., ?rum, H., Cho, M., Kole, R. Efficient and persistent splice switching by systemically delivered LNA oligonucleotides in mice. Mol. Ther. 2006;14:471C475. [PubMed] [Google Scholar]Saetrom, P., Heale, B.S.E., Snove O., Jr, Aagaard, L., Alluin, J., Rossi, J.J. Distance constraints between microRNA target sites dictate efficacy and cooperativity. Nucleic Acids Res. PLX-4720 2007;35:2333C2342. doi:?10.1093/nar/gkm133. [PMC free article] [PubMed] [CrossRef] [Google Scholar]Sazani, P., Gemignani, F., Kang, S.-H., Maier, M.A., Manoharan, M., Persmark, M., Bortner, D., Kole, R. Systemically delivered antisense oligomers upregulate gene expression in mouse tissues. Nat. Biotechnol. 2002;20:1228C1233. [PubMed] [Google Scholar]Suwanmanee, T., Sierakowska, H., Fucharoen, S., Kole, R. Repair of a splicing defect in erythroid cells from patients with -thalassemia/HbE disorder. Mol. Ther. 2002;6:718C726. [PubMed] [Google Scholar]Triboulet, R., Mari, B., Lin, Y.-L., Chable-Bessia, C., Bennasser, Y., Lebrigand, K., Cardinaud, B., Maurin, T., Barbry, P., Baillat, V., et al. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315:1579C1582. [PubMed] [Google Scholar]Turner, J.J., Arzumanov, A.A., Gait, M.J. Synthesis, cellular uptake and HIV-1 Tat-dependent microRNA miR-14 suppresses cell death and is required for normal fat metabolism. Curr. Biol. 2003;13:790C795. [PubMed] [Google Scholar]Xue-Wen, H., Jie, P., Xian-Yuan, A., Hong-Xiang, Z. Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA. J. Pept. Sci. 2007;13:220C226. [PubMed] [Google Scholar].