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The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice

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Title: The Insertion Timing of PEGylated Lipids to Galactosylated Lipoplexes Is Important for Liver-Selective Transfection in Mice
Authors: Fumoto, Shintaro / Taniguchi, Naoki / Ikai, Yuri / Yoshikawa, Naoki / Miyamoto, Hirotaka / Sasaki, Hitoshi / Hashida, Mitsuru / Kawakami, Shigeru / Nishida, Koyo
Issue Date: 14-Apr-2016
Publisher: Science Publishing Group
Citation: Gene and Cell Therapy, 1(1), pp.1-11; 2016
Abstract: In the present study, we demonstrated the importance of PEGylation timing of galactosylated liposome/plasmid DNA (pDNA) complexes (lipoplexes) for liver-selective transfection in mice. Because a fenestrated endothelium can be a barrier for penetration of lipoplexes though sinusoids, the particle size of lipoplexes is one of the determining factors for in vivo liver parenchymal cell (hepatocyte, PC)-selective transfection. Here, we found that syn-insertion, as a novel PEGylation timing, was useful to control the particle size of galactosylated lipoplexes. Syn-insertion of PEGylated lipids was performed by simple mixing of pDNA solution containing PEGylated lipids and dispersion of the cationic liposomes. Both syn- and pre-insertion of PEGylated lipids decreased the particle size of lipoplexes, whereas post-insertion did not. Moreover, syn-insertion of PEGylated lipids to galactosylated lipoplexes improved liver selectivity and the PC/non-parenchymal cell ratio of transgene expression after intravenous injection in mice. Hence, these data will be valuable for the design and preparation of PEGylated lipoplexes for gene targeting.
Keywords: Gene Therapy / PEGylation / Galactosylated Liposomes / Targeting / Hepatocyte
URI: http://hdl.handle.net/10069/36354
Rights: (c) 2016 Shintaro Fumoto et al. This article is distributed under Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/36354

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