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Jason D Tucker
Jason D Tucker
Tanzania
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Research Article
Tris[2-(Acryloyloxy)Ethyl]Isocyanurate Cross-Linked Polyethylenimine Enhanced Exon-Skipping of Antisense 2′-Omethyl Phosphorothioate Oligonucleotide in vitro and in vivo
Author(s): Mingxing Wang, Bo Wu, Jason D Tucker and Peijuan Lu Mingxing Wang, Bo Wu, Jason D Tucker and Peijuan Lu
Branched poly(ester amine)s (PEAs) based on tris[2-(acryloyloxy)ethyl]isocyanurate (TAEI) cross-linked low molecular weight polyethylenimine (LPEI, Mw: 0.8k/1.2k/2.0k) polymers have been evaluated for their ability to deliver antisense 2′-O-methyl phosphorothioate RNA (2′-OMePS) through in vitro and in dystrophic mdx mice. Almost all PEAs improved exon-skipping of 2′-OMePS both in vitro and in vivo. Especially the PEAs composed of PEI 2.0k (C series) enhanced 2′-OMePS delivery more effectively than PEI 0.8k or 1.2k-based series using a GFP reporter-based C2C12 myoblast culture system and in mdx mice. The highest efficiency of targeted exon-skipping of 2′-OMePS was obtained by PEA C14 [TAEI-PEI 2.0k (1:4)] with up to 6 fold increase compared with 2′-OMePS only in mdx mice via intramuscular injection without increased muscle damage. Enhanced exon-skip.. View More»
DOI: 10.4172/2157-7439.1000261