Monomolecular collapse of plasmid DNA into stable virus-like particles
Monomolecular collapse of plasmid DNA into stable virus-like particles
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DOI：
10.1073/pnas.95.4.1427
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发表时间：
1998-02-17
影响因子：
11.1
通讯作者：
Behr, JP
中科院分区：
文献类型：
--
作者：
Blessing, T;Remy, JS;Behr, JP
阳离子脂类被广泛应用于体外细胞转染法。然而，脂质/DNA复合体倾向于聚集成大的、多分散的颗粒混合物，这阻碍了它们在体内的使用。相反，阳离子洗涤剂不能介导细胞转导，但能够将单个DNA分子凝聚成离散的实体。我们只利用了这两种两亲性的有趣特征，通过两步形成稳定的核心粒子，使人联想到病毒。单独的阴离子质粒分子与精心定制的阳离子半胱氨酸基洗涤剂合作崩溃。然后，通过半胱氨酸洗涤剂在模板DNA上自发有氧二聚成半胱氨酸脂，得到的23 nm颗粒被简单地冻结。在生理条件下，球形颗粒的数量是单分散的，并在几天内保持稳定。加上负的表面电位，这些特性应该确保良好的组织扩散，并在静脉注射后从血流中逃逸。注射。
Cationic lipids are being widely used for cell transfection in vitro. The lipid/DNA complexes, however, tend to aggregate into large and polydisperse particle mixtures; this hampers their use in vivo. Cationic detergents, on the contrary, do not mediate cell transfection pel se, yet are capable of condensing individual DNA molecules into discrete entities. We have taken (only) the interesting features of both types of amphiphiles for the two-step formation of stable core particles reminiscent of viruses. Individual anionic plasmid molecules were cooperatively collapsed with a carefully tailored cationic cysteine-based detergent. The resulting 23-nm particles were then simply "frozen" by spontaneous aerobic dimerization of the cysteine-detergent into a cystine-lipid on the template DNA. The population of spherical particles is monodisperse and stable over days, in physiological conditions. Together with a negative surface potential, these properties should ensure good tissue dissemination and escape from the blood stream after i.v. injection.