Audouy S, Hoekstra D
Department of Membrane Cell Biology, Faculty of Medical Sciences, University of Groningen, The Netherlands.
Mol Membr Biol. 2001 Apr-Jun;18(2):129-43.
Recent rapid developments in genomics will likely lead to a rapid expansion in identifying defective genes causing a variety of diseases, implying a vast increase in the number of therapeutic targets. Treatment of such diseases may include strategies ranging from gene delivery and replacement to antisense approaches. For successful development of gene therapies, a minimal requirement involves the engineering of appropriate gene- or oligonucleotide-carrier systems, which are necessary for protective purposes (against nucleases) and transport (to target tissue and cells in vivo). Further, they should also display the propensity to efficiently translocate the oligonucleotides and gene constructs into cells, via passage across several membrane barriers. The emphasis in this review will be on the use of cationic lipids for that purpose. Crucial to successful application of this sophisticated technology in vivo will be a need for a better understanding of fundamental and structural parameters that govern transfection efficiency, including the issues of cationic lipid/DNA complex assembly (with or without helper lipid), stability towards biological fluids, complex-target membrane interaction and translocation, and gene-integration into the nucleus. Biophysical and biochemical characterization of so-called lipoplexes, and their interaction with cells in vitro, are considered instrumental in reaching such insight. Here, most recent advances in cationic lipid-mediated gene delivery are discussed from such a perspective.
基因组学领域最近的快速发展可能会导致在识别导致各种疾病的缺陷基因方面迅速扩张，这意味着治疗靶点的数量将大幅增加。此类疾病的治疗策略可能包括从基因传递和替换到反义方法等各种手段。为了成功开发基因疗法，一个最基本的要求是构建合适的基因或寡核苷酸载体系统，这对于保护目的（抵御核酸酶）和运输（在体内运输到靶组织和细胞）来说是必需的。此外，它们还应表现出能够有效地将寡核苷酸和基因构建体穿过几个膜屏障转运到细胞内的倾向。本综述将重点关注为此目的使用阳离子脂质。要在体内成功应用这项复杂技术，关键在于更好地理解决定转染效率的基本和结构参数，包括阳离子脂质/DNA复合物组装（有无辅助脂质）、对生物流体的稳定性、复合物与靶膜的相互作用和转运以及基因整合到细胞核等问题。对所谓脂质体的生物物理和生化特性及其在体外与细胞的相互作用进行研究，被认为有助于获得此类见解。在此，将从这一角度讨论阳离子脂质介导的基因传递的最新进展。
