Audouy Sandrine A L, de Leij Lou F M H, Hoekstra Dick, Molema Grietje
Department of Membrane Cell Biology, Groningen University Institute for Drug Exploration, Groningen, The Netherlands.
Pharm Res. 2002 Nov;19(11):1599-605. doi: 10.1023/a:1020989709019.
After a decade of clinical trials, gene therapy seems to have found its place between excessive ambitions and feasible aims, with encouraging results obtained in recent years. Intracellular delivery of genetic material is the key step in gene therapy. Optimization of delivery vectors is of major importance for turning gene therapy into a successful therapeutic method. Nonviral gene delivery relies mainly on the complexes formed from cationic liposomes (or cationic polymers) and DNA, i.e., lipoplexes (or polyplexes). Many lipoplex formulations have been studied, but in vivo activity is generally low compared to that of viral systems. This review gives a concise overview of studies on the application of cationic liposomes in vivo in animal models of diseases and in clinical studies. The transfection efficiency, the pharmacokinetic and pharmacodynamic properties of the lipid-DNA complexes, and potentially relevant applications for cationic liposomes are discussed. Furthermore, the toxicity of, and the induction of an inflammatory response in association with the administration of lipoplexes are described. Increasing understanding of lipoplex behavior and gene transfer capacities in vivo offers new possibilities to enhance their efficiency and paves the path to more extensive clinical applications in the future.
经过十年的临床试验，基因治疗似乎已在过度的雄心与可行的目标之间找到了自己的位置，近年来取得了令人鼓舞的成果。遗传物质的细胞内递送是基因治疗的关键步骤。优化递送载体对于将基因治疗转变为一种成功的治疗方法至关重要。非病毒基因递送主要依赖于由阳离子脂质体（或阳离子聚合物）与DNA形成的复合物，即脂质体复合物（或多聚体复合物）。许多脂质体复合物配方已被研究，但与病毒系统相比，其体内活性通常较低。本文综述了阳离子脂质体在疾病动物模型体内应用及临床研究的相关进展。文中讨论了脂质-DNA复合物的转染效率、药代动力学和药效学特性，以及阳离子脂质体潜在的相关应用。此外，还描述了脂质体复合物给药后的毒性及炎症反应诱导情况。对脂质体复合物在体内行为和基因转移能力的深入了解为提高其效率提供了新的可能性，并为未来更广泛的临床应用铺平了道路。
