Kawakami Shigeru
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Yakugaku Zasshi. 2008 Dec;128(12):1743-9. doi: 10.1248/yakushi.128.1743.
Recently several systems including viral and non-viral carriers that can be used to transfer foreign genetic material into cells have been developed with the aim of enhancing gene transfer in vivo. Non-viral vectors are relatively easy to produce in clinically relevant quantities, and associated with fewer safety concerns. Furthermore, synthetic non-viral vectors provide flexibility in formulation design and can be tailored to interact efficiency with DNA cargo and the specific route of vector injection, and can enhance delivery to specific tissues or cells through incorporation of a targeting ligand. Applying cell-specific targeting technology to liposomes would improve in vivo gene transfection efficacy and reduce any unexpected side-effects. Among the various receptors, asialoglycoprotein receptors and mannose receptors are the most promising for gene targeting since they exhibit high affinity and are rapidly internalized. Receptor-mediated delivery systems are able to introduce foreign DNA into specific cell types in vivo. Our group succeeded in the development of glycosylated cationic liposomes for cell-selective targeting of plasmid DNA, siRNA, and NFkappaB decoy based on the optimization of physicochemical properties of glycosylated liposome complex.
最近，为了提高体内基因转移效率，人们开发了几种包括病毒和非病毒载体在内的系统，可用于将外源遗传物质导入细胞。非病毒载体相对容易大量生产，且安全性问题较少。此外，合成非病毒载体在制剂设计上具有灵活性，可以根据与DNA货物的相互作用效率以及载体注射的特定途径进行定制，并且可以通过掺入靶向配体来增强对特定组织或细胞的递送。将细胞特异性靶向技术应用于脂质体将提高体内基因转染效率并减少任何意外的副作用。在各种受体中，去唾液酸糖蛋白受体和甘露糖受体最有希望用于基因靶向，因为它们具有高亲和力且能迅速内化。受体介导的递送系统能够将外源DNA导入体内特定的细胞类型。我们的研究小组基于糖基化脂质体复合物理化性质的优化，成功开发了用于细胞选择性靶向质粒DNA、小干扰RNA和核因子κB诱饵的糖基化阳离子脂质体。
