Cationic amphipathic histidine-rich peptides for gene delivery

摘要: Besides being a useful tool in research, gene transfer has high potential as treatment for variety of genetic and acquired diseases. However, order to enable become pharmaceutical, efficient safe methods delivery have be developed. We recently found that cationic amphipathic histidine-rich peptide antibiotics can efficiently deliver DNA into mammalian cells. Our lead compound, LAH4 (KKALLALALHHLAHLALHLALALKKA), demonstrated vitro transfection efficiencies comparable those commercially available reagents. Synthesis evaluation LAH mutants provided evidence the efficiency depends on number positioning histidine residues well pH at which in-plane transmembrane transition takes place. Moreover, recent results suggest binding complexes plasma membrane is mediated by heparan sulfate proteoglycans anionic phospholipids may involved endosomal destabilization process. Finally, we also describe this review rationale led development carrier biophysical allowed us propose model could explain way destabilizes bilayer.