Designer peptide delivery systems for gene therapy

Abstract

: Gene therapy has long been hailed as a revolutionary approach for the treatment of genetic diseases. The enthusiasm that greeted the harnessing of viruses for therapeutic DNA delivery has been tempered by concerns over safety. These concerns led to the development of alternative strategies for nucleic acid delivery to cells. One such strategy is the utilization of cationic peptides for the condensation of therapeutic DNA for delivery to its target. However, success of DNA as a therapy relies on its delivery to the nucleus of target cells, a process that is complicated by the many hurdles encountered following systemic administration. Non-viral peptide gene delivery strategies have sought inspiration from viruses in order to retain DNA delivering potency, but limit virulence. This review summarizes the progression of peptide-based DNA delivery systems, from rudimentary beginnings to the recent development of sophisticated multi-functional vectors that comprise distinct motifs with dedicated barrier evasion functions. The most promising peptides that achieve cell membrane permeabilization, endosomal escape and nuclear delivery are discussed.

DNA vaccination via RALA nanoparticles in a microneedle delivery system induces a potent immune response against the endogenous prostate cancer stem cell antigen

“…[16] To be efficacious in vivo, vectors must retain these characteristics at body temperature, and protect pDNA from degradation via serum nucleases. [17][18][19][20] Therefore the first aim of this study was to determine that complexing pPSCA to the RALA delivery peptide resulted in NPs with ideal properties for mediating transfection. The RALA peptide has previously been demonstrated to form nanoscale complexes with pDNA, which are stable at RT, resistant to degradation within the serum, and enhance transfection efficacy in vitro and in vivo.…”

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

“…One of the most versatile and promising in vivo gene transfer vectors with cell penetrating properties are peptiplexes based on various lengths of oligoarginine [135]. The merits of utilizing positively charged arginine for gene delivery, with superior cell penetrating ability compared to lysine, are firmly supported by numerous studies [136,137]. For example, R15 peptiplexes delivering One of the most versatile and promising in vivo gene transfer vectors with cell penetrating properties are peptiplexes based on various lengths of oligoarginine [135].…”

Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

“…poly-L-lysine (PLL), poly(ethylenimine) (PEI)) and lipids (e.g., 1,2-dioleoyloxy-3-(trimethylammonio)propane (DOTAP)) have been used to package DNA forming polyplexes and lipoplexes respectively [13]. However, problems with nonbiodegradability and toxicity [59] have led to increasing attention being paid to delivery systems which are biocompatible, have low toxicity and are easily fine-tuned [60,61]. DNA nanostructures have been developed as a non-cationic delivery platform compatible with biological systems.…”