Kim, Younghoon and Tewari, Manorama and Pajerowski, J. David and Cai, Shenshen and Sen, Shamik and Williams, Jason and Sirsi, Shashank and Lutz, Gordon and Discher, Dennis E. (2009) Polymersome delivery of siRNA and antisense oligonucleotides. Journal of Controlled Release, 134 (2). 132 - 140.
Full text is not hosted in this archive but may be available via the Official URL, or by requesting a copy from the corresponding author.
Official URL: http://www.sciencedirect.com/science/article/B6T3D...
siRNA and antisense oligonucleotides, AON, have similar size and negative charge and are often packaged for in vitro delivery with cationic lipids or polymers—but exposed positive charge is problematic in vivo. Here we demonstrate loading and functional delivery of RNAi and AON with non-ionic, nano-transforming polymersomes. These degradable carriers are taken up passively by cultured cells after which the vesicles transform into micelles that allow endolysosomal escape and delivery of either siRNA into cytosol for mRNA knockdown or else AON into the nucleus for exon skipping within pre-mRNA. Polymersome-mediated knockdown appears as efficient as common cationic-lipid transfection and about half as effective as Lenti-virus after sustained selection. For AON, initial results also show that intramuscular injection into a mouse model of muscular dystrophy leads to the expected protein expression, which occurs along the entire length of muscle. The lack of cationic groups in antisense polymersomes together with initial tests of efficacy suggests broader utility of these non-viral carriers.
|Uncontrolled Keywords:||Polymersome; siRNA; AON; Antisense; Exon skipping; Muscular dystrophy|
|Subjects:||Biomedical Science > Nanomedicine|
|Deposited On:||28 Jul 2009 14:47|
|Last Modified:||28 Jul 2009 14:47|
Repository Staff Only: item control page