γ-Polyglutamic acid-coated vectors for effective and safe gene therapy
γ-Polyglutamic acid-coated vectors for effective and safe gene therapy
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DOI：
10.1016/j.jconrel.2009.11.010
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发表时间：
2010-03-19
影响因子：
10.8
通讯作者：
Sasaki, Hitoshi
中科院分区：
文献类型：
--
作者：
Kurosaki, Tomoaki;Kitahara, Takashi;Sasaki, Hitoshi
在本研究中，我们开发了一些新的基因载体，包被阳离子复合物与γ-聚谷氨酸（γ-PGA）的有效和安全的基因治疗。以聚L-精氨酸盐酸盐（PLA）、聚L-赖氨酸氢溴酸盐（PLL）、N-[1-（2，3-二油基氧基）丙基]-N，N，N-三甲基氯化铵（DOTMA）-胆固醇（Chol）脂质体和DOTMA-二油基磷脂酰乙醇胺（DOPE）脂质体为载体，构建了pDNA阳离子复合物。阳离子配合物在黑色素瘤B16-F10细胞中显示出高基因表达和强细胞毒性。阳离子配合物对红细胞也有很强的毒性。另一方面，γ-PGA能够包覆所有阳离子复合物并形成稳定的带负电荷的纳米级颗粒。这些γ-PGA包被的复合物具有高基因表达，对红细胞无细胞毒性和毒性。在体内转染实验中，复合物在静脉内注射后在肺组织中显示出超过10（5）RLU/g的高转染效率，尽管γ-PGA包被的复合物在脾中显示出高值。在脾和肺中观察到脂质复合物和γ-PGA包被的脂质复合物的高转染效率。因此，γ-PGA包被的载体可用于临床基因治疗。(C)2009 Elsevier B. V.保留所有权利。
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. (C) 2009 Elsevier B.V. All rights reserved.