Non-viral peptide-based approaches to gene delivery

To achieve effective non-viral gene therapy, the control of in vitro and in vivo stability, cellular access, intracellular trafficking and nuclear retention of plasmids must be achieved. Inefficient endosomal release, stability against cytosolic nucleases, cytoplasmic transport and nuclear entry of plasmids are amongst some of the key limiting factors in the use of plasmids for effective gene therapy. Synthetic peptide-based gene delivery systems can be designed for DNA compaction, serum stability, cell-specific targeting, endosomolysis, cytoplasmic stability and nuclear transport. The stability of compacted DNA under physiological conditions can be enhanced by the use of hydrophilic polymers, such as polyethylene glycol. The aims of this review are to (i) explore theoretical and experimental aspects of DNA compaction, (ii) describe approaches for stabilizing compacted DNA, (iii) assess techniques used for characterization of compacted DNA, and (iv) review possible use of peptides for efficient gene transfer.