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Enhanced transfection efficacy of polyethylenimine by surface modification with arginine, lysine, and leucine

Aldawsari, Hibah Mobarak and Sundara Raj, Behin and Edrada-Ebel, Ruangelie and Blatchford, David and Tate, Rothwelle and Dufès, Christine (2010) Enhanced transfection efficacy of polyethylenimine by surface modification with arginine, lysine, and leucine. Controlled Release Society Newsletter, 27 (6). pp. 12-14.

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The potential of gene therapy is currently limited by the lack of delivery systems able to efficiently carry therapeutic DNA to their site of action. Non-viral vectors are receiving increasing attention as gene delivery vehicles due to the limitations associated with viral vectors in terms of safety and immunogenicity. Unfortunately, their use is hampered by their lower transfection efficacy compared with viral systems. The present study investigates the possibility of improving transfection by grafting amino acids onto the surface of a non-viral gene delivery system. We chose to use the amino acids arginine, lysine, and leucine because they have been reported to enhance transportation into cells (1–3). As a model delivery system, we chose to use the polymer polyethylenimine (PEI), because it has been widely used for non-viral transfection in vitro and in vivo and combines strong DNA compaction capacity with an intrinsic endosomolytic activity known as the proton sponge effect (4–5). It is hypothesized that arginine-, lysine-, and leucine-bearing polyethylenimine would lead to improved transfection efficacy through the synergistic action of the proton sponge effect and hydrophobic interactions with the cellular membranes. The objectives of this study, therefore, are 1) to prepare and characterize arginine-, lysine-, and leucine-bearing polyethylenimine; 2) to evaluate their transfection and therapeutic efficacies in vitro on the A431 human epidermoid carcinoma cell line; and 3) to evaluate their transfection efficacy in vivo after intravenous administration in mice bearing A431 tumours.