An Amphiphilic Peptide with Cell Penetrating Sequence for Highly Efficient Gene Transfection

Development of efficient gene vectors is of great importance for promoting gene therapy. An amphiphilic peptide with the sequence of Ac-RGDGPLGLAGI3GR8-NH2 (RR-22) has been designed for gene delivery applications. The peptide is a bolaform amphiphile in nature by having two charged segments distributed at the two terminals and a hydrophobic segment in the middle. The R8 segment is a highly positively charged cell membrane-penetrating sequence that can bind strongly with both DNA and cell membranes. The hydrophobic segment can provide hydrogen bonding and hydrophobic interactions to drive peptide self-assembly. With these characteristics, RR-22 can induce efficient DNA condensation into compact nanoparticles by synergistic effects of electrostatic interaction and peptidic association, a mechanism that is different from those of cationic polyelectrolytes and surfactants. The condensates can resist enzymatic degradation of DNA and ensure successful DNA delivery into cells. More specifically, RR-22 can mediate a quite high level of gene transfection as confirmed by using pEGFP-N2 as a reporter gene to express green fluorescent protein (GFP) in 293E cells. This study illustrates a potential design strategy for developing peptidic gene delivery systems with enhanced DNA condensing ability and gene transfection level.