Introduction of a disulfide bond into a cationic lipid enhances transgene expression of plasmid DNA.
Introduction of a disulfide bond into a cationic lipid enhances transgene expression of plasmid DNA.
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DOI：
10.1006/bbrc.1997.7923
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发表时间：
1998-01
影响因子：
3.1
通讯作者：
F. Tang;J. Hughes
中科院分区：
文献类型：
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作者：
F. Tang;J. Hughes
介绍了一种合成含二硫离子阳离子脂质的简便方法。合成了1,2-二酰基-sn-甘油-3-琥珀酰-2-羟乙基二硫鸟氨酸缀合物（DOGSDSO）脂质体，并与DOPE联合制备脂质体。选择二硫键的基本原理是产生一种脂质，这种脂质可以在细胞的细胞质中选择性地不稳定。DOGSDSO的二硫键被还原介质劈裂，导致脂质体/DNA复合物的不稳定，因此与不含二硫的类似物相比，pDNA的释放增加。二硫键的引入增加了模型动物细胞系的转染活性。比较了DOTAP、DOGSDSO及其类似物在3种细胞系中的转染活性和毒性。使用DOGSDSO/DOPE产生的转基因（如荧光素酶）的数量大于DOTAP/DOPE，比其非二硫类似物高出50倍。结果表明，含二硫化物阳离子脂质体可作为优良的基因转染载体。
We have introduced a convenient method of synthesis for disulfide-containing cationic lipids. The lipid, 1,2-dioleoyl-sn-glycero-3-succinyl-2-hydroxyethyl disulfide ornithine conjugate (DOGSDSO), was synthesized and used to prepare liposomes in combination with DOPE. The rationale behind the selection of the disulfide bond was to produce a lipid which could be selectively destabilized within the cytosol of the cell. The disulfide bond of DOGSDSO was shown to be cleaved by reductive media leading to destabilization of the liposome/DNA complex, thus increasing the release of pDNA compared to a non-disulfide-containing analog. The introduction of a disulfide bond increases the transfection activity using model animal cell lines. The transfection activity and toxicity of DOTAP, DOGSDSO and its analog in three cell lines were compared. The amount of transgene (e.g. luciferase) produced with the use of DOGSDSO/DOPE was greater than that of DOTAP/DOPE and up to 50 times more than that of its non-disulfide analog. The results indicate disulfide-containing cationic liposomes may act as excellent vectors for gene transfection.