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.
雑誌名
Journal of controlled release : official journal of the Controlled Release Society
巻
142
号
3
ページ
404 - 410
発行年
2010-03-19
出版者
Elsevier B.V.
ISSN
01683659
EISSN
1873-4995
書誌レコードID
AA10458678@@@AA1153173X
PubMed番号
19931327
DOI
10.1016/j.jconrel.2009.11.010
権利
Copyright c 2009 Elsevier B.V. All rights reserved.
著者版フラグ
author
引用
Journal of controlled release, 142(3), pp.404-410; 2010
γ-Polyglutamic acid-coated vectors for effective and safe gene therapy.
JCR142_404.pdf
(624.09KB)
NAOSITEについて