Arima Hidetoshi
Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan.
Yakugaku Zasshi. 2004 Jul;124(7):451-64. doi: 10.1248/yakushi.124.451.
Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via nonviral routes has become more desirable and advantageous. In particular, polycation complexes with DNA (polyplex) are attractive nonviral vectors. To design novel polycationic vectors, we prepared polyamidoamine starburst dendrimer (dendrimer) conjugates with three cyclodextrins (CDE conjugates) and three generations (G2, G3, and G4) of dendrimers. Of seven CDE conjugates, an alpha-CDE conjugate (G3) with an average degree of substitution (DS) of alpha-CyD of 2.4 [alpha-CDE conjugate (G3, DS 2.4)] showed greater gene transfer activity than dendrimers and other alpha-CDE conjugates with less cytotoxicity. These results suggest the potential use of alpha-CDE conjugate (G3, DS 2.4) as a polycationic vector in vitro and in vivo. Herein, I review a recent polyfection method, with special focus on alpha-CDE conjugate (G3, DS 2.4).
由于对病毒DNA递送系统的毒性和免疫原性的担忧日益增加,通过非病毒途径进行DNA递送变得更具吸引力和优势。特别是,与DNA形成的聚阳离子复合物(多聚体)是有吸引力的非病毒载体。为了设计新型聚阳离子载体,我们制备了与三种环糊精结合的聚酰胺胺星型树枝状大分子(树枝状大分子)共轭物(CDE共轭物)以及三代(G2、G3和G4)树枝状大分子。在七种CDE共轭物中,α-环糊精平均取代度(DS)为2.4的α-CDE共轭物(G3)[α-CDE共轭物(G3,DS 2.4)]显示出比树枝状大分子和其他细胞毒性较小的α-CDE共轭物更高的基因转移活性。这些结果表明α-CDE共轭物(G3,DS 2.4)在体外和体内作为聚阳离子载体的潜在用途。在此,我综述了一种近期的多转染方法,特别关注α-CDE共轭物(G3,DS 2.4)。