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

Kwok, Albert, McCarthy, David, Hart, Stephen L. and Tagalakis, Aristides (2016) Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA. Chemical Biology and Drug Design, 87 (5). pp. 747-763. ISSN 1747-0277 DOI https://doi.org/10.1111/cbdd.12709

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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.

Item Type: Article
Uncontrolled Keywords: biophysical characteristics, DNA delivery, gene therapy, oligolysine peptide, RNA interference, siRNA delivery
Subjects: Q Science > QR Microbiology
R Medicine > RS Pharmacy and materia medica
Divisions: Biology
Date Deposited: 19 Apr 2018 10:55
URI: http://repository.edgehill.ac.uk/id/eprint/10248

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