Synthesis of polyallylamine derivatives and their use as gene transfer vectors in vitro

Cationic polymers possessing primary amine groups are inefficient in transf erring nucleic acids into eukaryotic cells. With appropriate chemical modif ication, namely glycolylation of the amine groups of polylysine and polyall ylamine, the actual number of free amino groups was decreased, hydrophilic residues were introduced, and the cytotoxicity of both polymers decreased s ignificantly. Furthermore, in the case of polyallylamine, its ability to me diate gene transfer into cells increased by several orders of magnitude. Tr ansfection efficiency was found to be dependent on the substitution level o f amino groups and reached highest levels in the presence of lysosomotropic and/or fusogenic agents. At optimal conditions, glycolylated PAM was shown to be as efficient as the linear polyethylenimine of 22 kDa.