Articles: oligonucleotides.
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Comment Letter
Factor XI antisense oligonucleotide for venous thrombosis.
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Comment Letter
Factor XI antisense oligonucleotide for venous thrombosis.
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Ann. N. Y. Acad. Sci. · Apr 2015
Splicing regulation in spinal muscular atrophy by an RNA structure formed by long-distance interactions.
Humans carry two copies of the survival motor neuron gene: SMN1 and SMN2. Loss of SMN1 coupled with skipping of SMN2 exon 7 causes spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. Our discovery of intronic splicing silencer N1 (ISS-N1) is a promising target, currently in a phase III clinical trial, for an antisense oligonucleotide-mediated splicing correction in SMA. ⋯ Located in the middle of intron 7, the 3' strand of ISTL1 falls within an inhibitory region that we term ISS-N2. We demonstrate that an antisense oligonucleotide-mediated sequestration of ISS-N2 fully corrects SMN2 exon 7 splicing and restores high levels of SMN in SMA patient cells. These results underscore the therapeutic potential of the regulatory information present in a secondary and high-order RNA structure of a human intron.
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Arthritis Res. Ther. · Mar 2015
Randomized Controlled Trial Multicenter StudyResults of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis.
This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRPRx), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA). ⋯ In this study, ISIS-CRPRx selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear.
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Randomized Controlled Trial Multicenter Study
Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease.
Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. ⋯ We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).