Numerous barriers, both extracellular and intracellular, hinder successful and efficient nonviral nucleic acid delivery. Due to their small size and ability to specifically recognize and interact with molecular targets, peptides can be incorporated as modular elements into synthetic nucleic acid delivery systems to overcome many of these barriers. Three classes of peptides that have frequently been integrated as components in nucleic acid delivery systems include cell-penetrating peptides (CPPs), endosomal release peptides, and nuclear localization sequences (NLSs).Various additional classes of peptides show promise for enhancing nucleic acid delivery by targeting cell surface receptors, inhibiting nuclease activity, and directing nucleic acids toward intracellular targets. In addition to a review of the various existing approaches to peptide-enhanced nucleic acid delivery, this article will discuss strategies for the development of new peptides and approaches for the incorporation of these peptides into nucleic acid delivery systems.
