背景:与病毒载体相比,许多天然与合成的阳离子类脂以脂质体的形式用于基因转移,具有无免疫原性、易生产、质粒免受核酸酶降解和无致瘤性等优点,并且作为病毒载体的有效替代物,阳离子脂质体能用于细胞的体内和体外转染。目的:介绍阳离子脂质体介导的基因转移机制研究进展。方法:由第一作者用计算机检索中国期刊全文数据库(CNKI:1987/2010)和PubMed(1987/2010)数据库,检索词分别为"基因治疗、阳离子脂质体、基因转移、机制"和"gene therapy,cationic liposome,gene transfer,mechanism",语言分别设定为中文和英文。从阳离子脂质体基因转染和基因转移机制进行总结,综述了阳离子脂质体介导的基因转移机制。结果与结论:共检索到108篇,按纳入和排除标准对文献进行筛选,共纳入20篇文章。综述了阳离子脂质体介导的基因转移机制,包括阳离子脂质体/DNA复合物的形成、细胞吸收、内含体释放和复合物解体以及细胞核摄入等方面的研究内容。结果提示,对类脂构效关系和基因转移机制的研究,是提高阳离子脂质体转染效率和优化基因治疗的关键。
BACKGROUND:Compared with viral vector,many cationic lipids naturally occurred or synthesized have been used for gene transfer in the form of liposomes,which have the advantages of non-immunogenicity,simple production,plasmid protected against nuclease degradation and non-oncogenicity,etc.And cationic lipids as an effective alternative of viral vector,cationic liposomes can be used for cell transfection in vivo and in vitro.OBJECTIVE:To introduce research progress on mechanisms of cationic liposome-mediated gene transfer.METHODS:CNKI database from 1987 to 2010 and PubMed database from 1987 to 2010 were retrieved by the first author with computer.The index words were "gene therapy,cationic liposome,gene transfer,mechanism" in Chinese and English.Literatures were limited to Chinese and English languages.From cationic liposome gene transfer and gene transfer mechanisms were summarized,the cationic liposome-mediated gene transfer mechanisms were reviewed.RESULTS AND CONCLUSION:Totally 108 literature were retrieved and selected according to inclusion and exclusion criteria,20 of them were included.The cationic liposome-mediated gene transfer mechanisms were reviewed,including the formation of the cationic lipid /DNA complexes,cell uptake,inclusion body release,complex dissolution,and nucleus intake research.The results indicated that research on structure-activity relationship of lipids and the mechanism of gene transfer is the key to improve cationic liposome transfection efficiency and optimize gene therapy.