Effects of a Novel Archaeal Tetraether-Based Colipid on the In Vivo Gene Transfer Activity of Two Cationic Amphiphiles
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- 作者：Tony Le Gall ; Julie Barbeau ; Sylvain Barrier ; Mathieu Berchel ; Lo茂c Lemi猫gre ; Jelena Jefti膰 ; Cristelle Meriadec ; Franck Artzner ; Deborah R. Gill ; Stephen C. Hyde ; Claude F茅rec ; Pierre Lehn ; Paul-Alain Jaffr猫s ; Thierry Benvegnu ; Tristan Montier
- 刊名：Molecular Pharmaceutics
- 出版年：2014
- 出版时间：September 2, 2014
- 年：2014
- 卷：11
- 期：9
- 页码：2973-2988
- 全文大小：698K
- ISSN：1543-8392
文摘
Gene therapy for treating inherited diseases like cystic fibrosis might be achieved using multimodular nonviral lipid-based systems. To date, most optimizations have concerned cationic lipids rather than colipids. In this study, an original archaeal tetraether derivative was used as a colipid in combination with one or the other of two monocationic amphiphiles. The liposomes obtained, termed archaeosomes, were characterized regarding lipid self-assembling properties, macroscopic/microscopic structures, DNA condensation/neutralization/relaxation abilities, and colloidal stability in the presence of serum. In addition, gene transfer experiments were conducted in mice with lipid/DNA complexes being administered via systemic or local delivery routes. Altogether, the results showed that the tetraether colipid can provide complexes with different in vivo transfection abilities depending on the lipid combination, the lipid/colipid molar ratio, and the administration route. This original colipid appears thus as an innovative modular platform endowed with properties possibly beneficial for fine-tuning of in vivo lipofection and other biomedical applications.