Fenske D B, MacLachlan I, Cullis P R
Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada.
Curr Opin Mol Ther. 2001 Apr;3(2):153-8.
The development of vectors capable of treating systemic diseases is an important goal for gene therapy protocols. In order for a carrier system to preferentially accumulate at sites of systemic disease, such as tumors, sites of inflammation and sites of infection, the carrier must exhibit long circulation lifetimes following intravenous injection. Unfortunately, most gene delivery systems, including viral vectors as well as non-viral vectors, e.g., lipoplexes, polyplexes and lipopolyplexes, are rapidly cleared from the circulation and are preferentially taken up by the 'first-pass' organs such as liver, lung and spleen. Here we review recent literature concerning the ability of non-viral vectors to act as systemic gene therapy agents. The most promising systemic vectors are liposomal systems in which plasmid DNA is encapsulated within a lipid bilayer. The stabilized plasmid-lipid particle (SPLP) system, for example, exhibits circulation half-lives of the order of 6 h following intravenous injection, and preferentially accumulates in distal tumors with gene expression primarily localized to the tumor site.
开发能够治疗全身性疾病的载体是基因治疗方案的一个重要目标。为了使载体系统优先在全身性疾病部位（如肿瘤、炎症部位和感染部位）积累，载体在静脉注射后必须具有较长的循环寿命。不幸的是，大多数基因递送系统，包括病毒载体以及非病毒载体（如脂质体、多聚体和脂质多聚体），都会迅速从循环中清除，并优先被肝脏、肺和脾脏等“首过”器官摄取。在此，我们综述了有关非病毒载体作为全身性基因治疗剂能力的近期文献。最有前景的全身性载体是脂质体系统，其中质粒DNA被包裹在脂质双层内。例如，稳定化质粒-脂质颗粒（SPLP）系统在静脉注射后循环半衰期约为6小时，并优先在远端肿瘤中积累，基因表达主要定位于肿瘤部位。
