An amphiphilic peptide with cell penetrating sequence for highly efficient gene transfection

Key Words:DNA CONDENSATION; SUPRAMOLECULAR ASSEMBLIES; TRANSITION; DELIVERY; DESIGN; NANOSTRUCTURES; VECTORS; BINDING; MIMICS; COIL

Abstract:Development of efficient gene vectors is of great importance for promoting gene therapy. An amphiphilic peptide with the sequence of Ac-RGDGPLGLAGI(3)GR(8)-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 R-8 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.

Volume:590

Translation or Not:no