The delivery of nucleic acids to cells as well as the instability in blood are important subjects for successful in vivo gene therapies. The design of synthetic polycation as non-viral gene vectors has received considerable attention for the purpose of realizing in vivo gene therapy -4 Although numerous polycations have been designed and synthesized, the rational design of polymers as in vivo gene vector systems has not yet been established. The use of polycations with relatively low pKa values are mentioned as one of the guidelines. Polycations with low pKa values, such as polyethyleneimine (PEI) and polyamidoamine (PAMAM) dendrimer, exhibit a high transfection efficiency due to the buffering effect,5-8 and PEI and PAMAM dendrimer are marketed under the trade names of ExGene and SuperFect, respectively. However, these have relatively weak affinity to DNA compared with cationic polymers, such as poly(L-lysine) (PLL) having high pKa value. One looks forward to the design of polycations, which combines stable complex formation under physiological conditions and a buffering effect. Recently, Kataoka et al. reported the polyplex vectors from A-B-C type triblock copolymers with spatially ordered layering of the condensed pDNA and buffering units for enhanced intracellular gene delivery Such a molecular design, which produces a function share in each block of the copolymer, could be effective in realizing in vivo gene therapy. In this study, we have newly designed a head-tail type polycation block copolymer, which is composed of the PAMAM dendron as the head block and PLL as the tail block, as a non-viral gene vector. In the design of the block copolymer composed of polycation blocks with different pKa values as the gene vector, it is important that the pKa values of the polycation block with a relatively low pKa value be maintained even after the block copolymerization with different kind of polycations as well as the complexation with the pDNA. Consequently, the PAMAM dendron was selected as a buffering block with a low pKa value, since the tertiary amino groups in the interior of the PAMAM dendron cannot be easily influenced by another polycation block due to steric hindrance. It was expected that the head and tail blocks exhibit a buffering action and complexation
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