Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery

Helen O. McCarthy, Joanne McCaffrey, Cian M. McCrudden, Aleksey Zholobenko, Ahlam A. Ali, John W. McBride, Ashley S. Massey, Sreekanth Pentlavalli, Kun-Hong Chen, Grace Cole, Stephen P. Loughran, Nicholas J. Dunne, Ryan F. Donnelly, Victoria L. Kett, Tracy Robson

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)


The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were < 100 nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics.

Original languageEnglish
Pages (from-to)141-149
Number of pages9
JournalJournal of Controlled Release
Early online date01 Jul 2014
Publication statusPublished - 10 Sep 2014

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Copyright © 2014 Elsevier B.V. All rights reserved.


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