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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).

Polyfection as Nonviral Gene Transfer Method —Design of Novel Nonviral Vector Using α-Cyclodextrin—