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

Authors :
McCarthy HO
McCaffrey J
McCrudden CM
Zholobenko A
Ali AA
McBride JW
Massey AS
Pentlavalli S
Chen KH
Cole G
Loughran SP
Dunne NJ
Donnelly RF
Kett VL
Robson T
Source :
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2014 Sep 10; Vol. 189, pp. 141-9. Date of Electronic Publication: 2014 Jul 01.
Publication Year :
2014

Abstract

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 <100nm, 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.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-4995
Volume :
189
Database :
MEDLINE
Journal :
Journal of controlled release : official journal of the Controlled Release Society
Publication Type :
Academic Journal
Accession number :
24995949
Full Text :
https://doi.org/10.1016/j.jconrel.2014.06.048