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

Albert Kwok, David McCarthy, Stephen L. Hart, Aristides Tagalakis

Research output: Contribution to journalArticle

13 Citations (Scopus)
78 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)747-763
JournalChemical Biology and Drug Design
Volume87
Issue number5
Early online date1 Feb 2016
DOIs
Publication statusE-pub ahead of print - 1 Feb 2016

Keywords

  • biophysical characteristics
  • DNA delivery
  • gene therapy
  • oligolysine peptide
  • RNA interference
  • siRNA delivery

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