Abstract
Since its discovery, small interfering RNA (siRNA) has revolutionised the field of gene silencing therapy because of its great potential in targeting diseases that were considered untreatable. Although several siRNA drugs are already in the market, many challenges remain to be addressed before siRNA therapies can realise their full potential including extra-hepatic delivery and improved endosomal escape. Dendritic polypeptides are attractive carriers for siRNA because of their wide range of defined structures that can be made. In this work, we report the on-going development of histidylated poly(lysine) dendrimers (G3KH) as carriers for siRNA. Histidine-capped lysine dendrimers were synthesised via HBTU/HOBt coupling reaction in solution. 1H NMR data confirms the structure of G3KH dendrimers; however, although traces of impurities were also observed. Histidylated lysine dendrimers could efficiently condense short double-strand DNA oligos (used as a model for siRNA) to form cationic nanoparticles of less than 100 nm in size
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