ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Therapeutic Potential of OMe-PS-miR-29b1 for Treating Liver Fibrosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
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- Liver fibrosis pathologies and potentials of RNA based therapeutics modalities.Drug delivery and translational research · 2024Review
- Nanocarrier-Mediated Delivery of MicroRNAs for Fibrotic Diseases.Molecular diagnosis & therapy · 2024Review
- Anti-miR-96 and Hh pathway inhibitor MDB5 synergistically ameliorate alcohol-associated liver injury in mice.Biomaterials · 2023Article
- Recent advances in drug delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Nanoparticle Delivery of Novel PDE4B Inhibitor for the Treatment of Alcoholic Liver Disease.Pharmaceutics · 2022Article
- The regulatory roles of microRNAs toward pathogenesis and treatments in Huntington's disease.Journal of biomedical science · 2021Review
- Genetically blockingMolecular therapy. Methods & clinical development · 2021Article
- Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy.Science advances · 2020Article
- Unveiling ncRNA regulatory axes in atherosclerosis progression.Clinical and translational medicine · 2020Review
- Liver-targeted delivery of TSG-6 by calcium phosphate nanoparticles for the management of liver fibrosis.Theranostics · 2020Article
- The use of micelles to deliver potential hedgehog pathway inhibitor for the treatment of liver fibrosis.Theranostics · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trans-differentiation of quiescent hepatic stellate cells (HSCs) into active myofibroblasts secretes excess amounts of extracellular matrix (ECM) proteins. miR-29b1 has the potential to treat liver fibrosis, because it targets several profibrotic genes. We previously demonstrated that miR-29b1 and the hedgehog (Hh) pathway inhibitor GDC-0449 could, together, inhibit the activation of HSCs and ECM production in common bile-duct-ligated (CBDL) mice. Herein, we determined the effect of chemical modifications of miR-29b1 on its stability, immunogenicity, and Argonaute-2 (Ago2) loading in vitro, after modifying its antisense strand with phosphorothioate (PS-miR-29b1), 2'-O-methyl-phosphorothioate (OMe-miR-29b1), locked nucleic acid (LNA-miR-29b1), and N,N'-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine (ZEN-miR-29b1). Chemical modifications significantly improved stability of miR-29b1 in 50% FBS. Among all the modified miRNAs tested, OMe-PS-miR-29b1 showed the highest stability with low immunogenicity, without the loss of efficacy in vitro. Therefore, OMe-PS-miR-29b1 was complexed with poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-tetraethylenepentamine (mPEG-b-PCC-g-DC-g-TEPA) cationic micelles, and anti-fibrotic efficacy was evaluated in CBDL mice. There was a significant improvement in liver histology and decrease in the levels of injury markers. Further, mRNA/protein levels of collagen, α-SMA, and TIMP-1 were significantly lower for the OMe-PS-miR-29b1-loaded micelles compared to miR-29b1-loaded micelles. In conclusion, micellar delivery of OMe-PS-miR-29b1 is a promising strategy to treat liver fibrosis.
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