Engineering Peptide-based Carriers for Drug and Gene Delivery

Abstract

Recent research efforts have focused on the optimization of cell delivery systems with the aims of increasing cell specificity, incorporating organelle targeting and improving overall delivery efficiency. Peptides and proteins represent new and innovative strategies to meet these targets. The advantages of peptides are manyfold: they can condense DNA into compact particles for transport, disrupt the endosomal membrane, escape proteasomal degradation, traffic therapeutic molecules of various size, charge, and function to targeted intracellular compartments, and can have reduced cytotoxicity and immunogenicity. These properties can be part of a single peptide or the result from the conjugation of different peptides. Silk, a structural protein, is well known for its biodegradability and biocompatibility and can be tailored for specific design features via genetic engineering. With tunable structure, chemistry, and mechanical properties for silk proteins derived from spiders and insects, modified or recombinant silk proteins can be utilized in various biomedical applications such as for the design of gene delivery systems. This review summarizes the diversity and application of peptides and silk proteins to mediate intracellular delivery of genes and drugs.