Conclusion
Novel fusion peptides could successfully enhance siRNA penetration into
cells via a self-assembled complex and resultantly induced mRNA
knockdown similar to or better than those of commercialized
Lipofectamine™ 2000. The efficiency of mRNA knockdown was
synergistically affected by high cellular uptake efficiency, and higher
complex stability improved by the increase of arginine length.
Co-localization and cellular internalization of siRNA/S-R15 complexes
were confirmed peripherally around the nucleus. The primary endocytosis
pathway of the siRNA/S-R15 complex was identified as lipid raft-mediated
endocytosis. Also, the biosafety of each fusion peptide was confirmed by
the cytotoxicity test. Therefore, the safe, stable, and straightforward
complex strategy was expected to become a potent and efficient gene
delivery platform to treat various target diseases through gene therapy.