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2 results on '"2′-OMePS"'

1. Saponins enhance exon skipping of 2′-O-methyl phosphorothioate oligonucleotide in vitro and in vivo

Author

Wang M, Wu B, Shah SN, Lu P, and Lu Q

Subjects
Antisense delivery, 2′-OMePS, Exon-skipping, Saponin, Muscular dystrophy, Therapeutics. Pharmacology, RM1-950
Abstract

Mingxing Wang, Bo Wu, Sapana N Shah, Peijuan Lu, Qilong Lu McColl-Lockwood Laboratory for Muscular Dystrophy Research, Department of Neurology, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203, USA Background: Antisense oligonucleotide (ASO)-mediated exon skipping has been feasible and promising approach for treating Duchenne muscular dystrophy (DMD) in preclinical and clinical trials, but its therapeutic applications remain challenges due to inefficient delivery. Methods: We investigated a few Saponins for their potential to improve delivery performance of an antisense 2′-Omethyl phosphorothioate RNA (2′-OMePS) in muscle cells and in dystrophic mdx mice. This study was carried out by evaluating these Saponins’ toxicity, cellular uptake, transduction efficiency in vitro, and local delivery in vivo for 2′-OMePS, as well as affinity study between Saponin and 2′-OMePS. Results: The results showed that these Saponins, especially Digitonin and Tomatine, enhance the delivery of 2′-OMePS with comparable efficiency to Lipofectamine 2k (LF-2k)-mediated delivery in vitro. Significant performance was further observed in mdx mice, up to 10-fold with the Digitonin as compared to 2′-OMePS alone. Cytotoxicity of the Digitonin and Glycyrrhizin was much lower than LF-2k in vitro and not clearly detected in vivo under the tested concentrations. Conclusion: This study potentiates Saponins as delivery vehicle for 2′-OMePS in vivo for treating DMD or other diseases. Keywords: antisense delivery, 2′-OMePS, exon skipping, saponin, muscular dystrophy

Published
2018

2. Saponins enhance exon skipping of 2′-O-methyl phosphorothioate oligonucleotide in vitro and in vivo

Author

Qilong Lu, Bo Wu, Mingxing Wang, Sapana N. Shah, and Peijuan Lu

Subjects
muscular dystrophy, 0301 basic medicine, Cell Survival, Duchenne muscular dystrophy, antisense delivery, Molecular Conformation, Phosphorothioate Oligonucleotides, Pharmaceutical Science, Pharmacology, Cell Line, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Drug Delivery Systems, In vivo, 2′-OMePS, Drug Discovery, medicine, Animals, Glycyrrhizin, Cytotoxicity, saponin, Original Research, Drug Carriers, Drug Design, Development and Therapy, Dose-Response Relationship, Drug, Exons, Oligonucleotides, Antisense, Saponins, medicine.disease, Lipids, Exon skipping, In vitro, Mice, Inbred C57BL, carbohydrates (lipids), 030104 developmental biology, Digitonin, chemistry, Lipofectamine, exon skipping
Abstract

Mingxing Wang, Bo Wu, Sapana N Shah, Peijuan Lu, Qilong Lu McColl-Lockwood Laboratory for Muscular Dystrophy Research, Department of Neurology, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203, USA Background: Antisense oligonucleotide (ASO)-mediated exon skipping has been feasible and promising approach for treating Duchenne muscular dystrophy (DMD) in preclinical and clinical trials, but its therapeutic applications remain challenges due to inefficient delivery. Methods: We investigated a few Saponins for their potential to improve delivery performance of an antisense 2′-Omethyl phosphorothioate RNA (2′-OMePS) in muscle cells and in dystrophic mdx mice. This study was carried out by evaluating these Saponins’ toxicity, cellular uptake, transduction efficiency in vitro, and local delivery in vivo for 2′-OMePS, as well as affinity study between Saponin and 2′-OMePS. Results: The results showed that these Saponins, especially Digitonin and Tomatine, enhance the delivery of 2′-OMePS with comparable efficiency to Lipofectamine 2k (LF-2k)-mediated delivery in vitro. Significant performance was further observed in mdx mice, up to 10-fold with the Digitonin as compared to 2′-OMePS alone. Cytotoxicity of the Digitonin and Glycyrrhizin was much lower than LF-2k in vitro and not clearly detected in vivo under the tested concentrations. Conclusion: This study potentiates Saponins as delivery vehicle for 2′-OMePS in vivo for treating DMD or other diseases. Keywords: antisense delivery, 2′-OMePS, exon skipping, saponin, muscular dystrophy

Published
2018
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