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.
Keywords: Cell penetrating peptide; DNA; gene delivery; non-viral vectors; peptide.