Role of Peptide Molecular Conformation in Improving the Gene Delivery Efficiency of Liposomal Formulations

The study explored the impact of peptide conformations on the efficiency of nucleic acids transfection by designing two sets of linear (liKK and liRR) and cyclic peptides (cyKK and cyRR) with various sequences (KK: KKKKCRGDSCKKKK and RR: RRRRCLLLLCRRRR). Incorporating peptides in the liposome formulation improved gene transfection efficiency compared to the peptide and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) alone. The results revealed that adding linear peptides demonstrated a higher delivery efficiency in comparison to cyclic peptides in transfection formulations. Additionally, two effective groups of transfection formulations were established. The liKK/DOTAP/DOPE formulation proved exceptional at delivering mRNA, achieving a transfection efficiency of 93.3%, comparable to that of Lipofectamine 2000 (91.7%). In contrast, the liRR/DOTAP/DOPE formulation effectively delivered both pDNA and siRNA. The pDNA transfection efficiency reached 42.3%, closely matching Lipofectamine 2000 (43.9%), while the siRNA transfection efficiency hit 90.7%, surpassing Lipofectamine 2000’s performance (85.4%). The transfection efficiency of linear conformational formulations is superior to that of cyclic ones. Our research provides new options for liposome formulations and offers valuable insights for designing peptide-based gene delivery vectors with different conformations.