Structure-Function Correlations of Poly(Amido Amine)s for Gene Delivery

Poly(amido amine)s' (PAAs) versatility are nearly unique among stepwise polymers. Different functional groups can be easily introduced into these polymers to add functionality such as cell internalization, charge-shift, bioreducibility, "stealth" properties, and targeting moieties, while maintaining the bulk structural integrity of these polymers. The poly(amido amine)s are used as a unique research platform to elucidate their complex structure-function relationship. It is shown that guanidinium group, carboxyl group, disulfide bond, alkyl chain, branching, acetyl groups, benzoyl groups, and quaternary nicotinamide moieties can influence many steps of gene delivery, such as DNA condensation, cellular uptake, endosomal escape, nuclear entry, and finally gene expression. The authors systematically discuss the structure-function correlations of PAAs for gene delivery, and elaborate how the properties of polymers can be adjusted by changing the polymeric structure.