The AGMA1 polyamidoamine mediates the efficient delivery of siRNA

AbstractAGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1–5 and AGMA1–10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1–10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1–5 polyplexes were larger, about 100 nm in size. AGMA1–10 polyplexes, but not AGMA1–5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects. AGMA1–10 knocked down AKT-1 expression upon transfection with an AKT-1 specific siRNA. The polyplex entry mechanism was investigated and was mediated by macropinocytosis. In conclusion, AGMA1 has potential as an efficient, non-toxic tool for the intracellular delivery of siRNA and warrants further investigation.