alexa In vitro efficacy of morpholino-modified antisense oligomers directed against tumor necrosis factor-alpha mRNA.


Journal of Clinical & Experimental Cardiology

Author(s): Taylor MF, Paulauskis JD, Weller DD, Kobzik L

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Abstract Chemical modification of antisense oligonucleotides to increase nuclease resistance may improve their efficacy within enzyme-rich cellular targets (e.g. macrophages). We evaluated a panel of morpholino antisense oligomers (M-AS) for their ability to inhibit macrophage tumor necrosis factor-alpha (TNF-alpha) release and compared them to phosphodiester (O-AS) and phosphorothioate (S-AS) types of oligonucleotides. M-AS inhibited translation in vitro (rabbit reticulocyte lysate) of target mRNA at concentrations as low as 200 nM (e.g. percent inhibition by M-AS 2 at 0.2, 1.0, and 2.0 microM was 40.9 +/- 5.3\%, 50.2 +/- 4.6\%, and 57.7 +/- 3.6\%, respectively, n = 4, p This article was published in J Biol Chem and referenced in Journal of Clinical & Experimental Cardiology

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