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Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA

Kwok, A; McCarthy, D; Hart, SL; Tagalakis, AD; (2016) Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA. Chemical Biology and Drug Design , 87 (5) pp. 747-763. 10.1111/cbdd.12709. Green open access

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Abstract

The effects of lysine peptide lengths on DNA and siRNA packaging and delivery were studied using four linear oligolysine peptides with 8 (K8), 16 (K16), 24 (K24) and 32 (K32) lysines. Oligolysine peptides with 16 lysines or longer were effective for stable monodisperse particle formation and optimal transfection efficiency with plasmid DNA (pDNA) but K8 formulations were less stable under anionic heparin challenge and consequently displayed poor transfection efficiency. However, here we show that the oligolysines were not able to package siRNA to form stable complexes, and consequently siRNA transfection was unsuccessful. These results indicate that the physical structure and length of cationic peptides, and their charge ratios are critical parameters for stable particle formation with pDNA and siRNA and that without packaging, delivery and transfection cannot be achieved. This article is protected by copyright. All rights reserved.

Type: Article
Title: Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/cbdd.12709
Publisher version: http://dx.doi.org/10.1111/cbdd.12709
Language: English
Additional information: © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: DNA delivery, RNA interference, biophysical characteristics, gene therapy, oligolysine peptide, siRNA delivery
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1476795
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