Kirby Anthony J, Camilleri Patrick, Engberts Jan B F N, Feiters Martin C, Nolte Roeland J M, Söderman Olle, Bergsma Mark, Bell Paul C, Fielden Matthew L, García Rodríguez Cristina L, Guédat Philippe, Kremer Andreas, McGregor Caroline, Perrin Christele, Ronsin Gaël, van Eijk Marcel C P
University Chemical Laboratory, Cambridge CB2 1EW, UK.
Angew Chem Int Ed Engl. 2003 Apr 4;42(13):1448-57. doi: 10.1002/anie.200201597.
The superior surfactant properties of cationic gemini surfactants are applied to the complex problem of introducing genes into cells. Of almost 250 new compounds tested, of some 20 different structural types, a majority showed very good transfection activity in vitro. The surfactant is shown to bind and compact DNA efficiently, and structural studies and calculations provide a working picture of the "lipoplex" formed. The lipoplex can penetrate the outer membranes of many cell types, to appear in the cytoplasm encapsulated within endosomes. Escape from the endosome--a key step for transfection--may be controlled by changes in the aggregation behavior of the lipoplex as the pH falls. The evidence suggests that DNA may be released from the lipoplex before entry into the nucleus, where the new gene can be expressed with high efficiency.
阳离子双子表面活性剂卓越的表面活性剂性能被应用于将基因导入细胞这一复杂问题。在测试的近250种新化合物中，约20种不同结构类型的化合物中，大多数在体外表现出非常好的转染活性。该表面活性剂能有效结合并压缩DNA，结构研究和计算提供了所形成“脂质体复合物”的工作模型。脂质体复合物可穿透多种细胞类型的外膜，出现在内体包裹的细胞质中。从内体逃逸——转染的关键步骤——可能受脂质体复合物在pH值下降时聚集行为变化的控制。有证据表明，DNA可能在进入细胞核之前从脂质体复合物中释放出来，新基因可在细胞核中高效表达。
