title: Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA.
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.
authors.affiliation: Experimental and Personalised Medicine Section, UCL Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Kwok
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: David
authors.initials: D
authors.lastname: McCarthy
authors.affiliation: Experimental and Personalised Medicine Section, UCL Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hart
authors.affiliation: Experimental and Personalised Medicine Section, UCL Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
authors.forename: Aristides D
authors.initials: AD
authors.lastname: Tagalakis
mesh_terms: D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D014162:Transfection
chemical_list: D010455:Peptides; D034741:RNA, Small Interfering; D004247:DNA; D008239:Lysine
keywords: DNA delivery; RNA interference; biophysical characteristics; gene therapy; oligolysine peptide; siRNA delivery