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γ-Polyglutamic acid-coated vectors for effective and safe gene therapy.

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Title: γ-Polyglutamic acid-coated vectors for effective and safe gene therapy.
Authors: Kurosaki, Tomoaki / Kitahara, Takashi / Kawakami, Shigeru / Higuchi, Yuriko / Yamaguchi, Ayumi / Nakagawa, Hiroo / Kodama, Yukinobu / Hamamoto, Tomoyuki / Hashida, Mitsuru / Sasaki, Hitoshi
Issue Date: 19-Mar-2010
Publisher: Elsevier B.V.
Citation: Journal of controlled release, 142(3), pp.404-410; 2010
Abstract: In the present study, we developed some novel gene delivery vectors, coated cationic complexes with gamma-polyglutamic acid (gamma-PGA) for effective and safe gene therapy. Cationic complexes were constructed with pDNA and cationic vectors, such as poly-L-arginine hydrochloride (PLA), poly-L-lysine hydrobromide (PLL), N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol (Chol) liposomes, and DOTMA-dioleylphosphatidylethanolamine (DOPE) liposomes. The cationic complexes showed high gene expression with strong cytotoxicity in melanoma B16-F10 cells. The cationic complexes were also strongly toxic to erythrocytes. On the other hand, the gamma-PGA was able to coat all cationic complexes and form stable nano-sized particles with negative charges. These gamma-PGA-coated complexes had high gene expression without cytotoxicity and toxicities to the erythrocytes. In in vivo transfection experiments, polyplexes showed high transfection efficiency over 10(5) RLU/g in the lung tissue after intravenous injection, although gamma-PGA-coated polyplexes showed a high value in the spleen. High transfection efficiency in lipoplexes and gamma-PGA-coated lipoplexes was observed in the spleen and lung. Thus, gamma-PGA-coated vectors are useful for clinical gene therapy.
Keywords: γ-Polyglutamic acid / Cationic liposome / Cationic polymer / Non-viral gene delivery / Ternary complex
URI: http://hdl.handle.net/10069/22673
ISSN: 01683659
DOI: 10.1016/j.jconrel.2009.11.010
PubMed ID: 19931327
Rights: Copyright © 2009 Elsevier B.V. All rights reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22673

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