3 years ago

Amphiphilic small peptides for delivery of plasmid DNAs and siRNAs

Amphiphilic small peptides for delivery of plasmid DNAs and siRNAs
Wooyoung Hur, Hanna Cho, Dong-Kwon Lim, Sean S-H Jeon, Taebo Sim, Eun-Kyoung Bang, Na Ly Tran
Although various delivery systems for nucleic acids have been reported, development of an efficient and non-toxic delivery carrier is still a key subject for gene therapy. In order to find new efficient delivery carriers for nucleic acids, we synthesized amphiphilic peptides composed of a guanidino group, an oleyl group, and a cysteine. We prepared both linear and branched types of peptides, and found that the linear peptides were superior to the branched peptides as nucleic acid carriers. Our study also suggested that the intermolecular cysteine disulfides might allow the linear peptides to form the optimal particle sizes with nucleic acids for cellular uptake. The incorporation of a benzoyl group to the linear peptide gave rise to smaller, less suitable particle size with plasmid DNA, which greatly reduced the efficiency of plasmid DNA delivery. On the other hand, the benzoyl modification maintained the optimal particle size with siRNA, and interestingly it significantly enhanced the siRNA delivery. The higher efficiency is because the hydrophobicity from the benzoyl group might assist in interacting with the hydrophobic cell membrane. This demonstrates that a small structural change can modulate the preference of the carriers. Our study may provide an insight designing efficient delivery carriers. This article is protected by copyright. All rights reserved. As novel nucleic acid carriers, linear and branched amphiphilic peptides were prepared. Each peptide was compared in terms of SNALP size, stability, and delivery activities for plasmid DNA (pDNA) and siRNA. Among the five peptides, a linear peptide H-RCL was an effective delivery carrier for both siRNA and pDNA. Introduction of a benzoyl group to H-RCL significantly enhanced siRNA delivery, but greatly reduced pDNA delivery. These demonstrated that a small structural modification of the peptides can modulate their delivery properties.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13122

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