Gene delivery by peptide-assisted transport

Abstract

The diverse amino acid chemistries and secondary structures in peptides provide ‘minimalist’ mimics of motifs in proteins and offer many ideal properties for targeted delivery approaches. Several non-viral vectors (polymers and lipids) have been studied for their potential applications in gene delivery. However, non-specific uptake, lack of targeting, inability to escape endosomes, and inefficient nuclear delivery limit their application. Peptide-assisted trafficking of non-viral vectors can potentially overcome these biological barriers to improve gene delivery through targeted uptake using key cell-surface receptors (e.g., integrins, growth factor receptors, and G-protein coupled receptors); membrane disruption for endosomal escape; and nuclear importation. Furthermore, the capacity of peptides to regulate spatio-temporal control over gene delivery opens multi-faceted avenues for effective gene delivery in a variety of complex applications. Rigorous on-going in vitro and in vivo studies utilizing peptides for targeted and microenvironment-sensitive gene delivery could promote their widespread clinical usage.