Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA. (1st February 2016)

• Record Type: Journal Article
• Authors: Kwok, Albert; McCarthy, David; Hart, Stephen L.; Tagalakis, Aristides D.
• Is Part Of: Chemical biology & drug design. Volume 87:Number 5(2016)
• Page Start: 747
• Page End: 763
• Publication Date: 2016-02-01
• Subjects: biophysical characteristics -- DNA delivery -- gene therapy -- oligolysine peptide -- RNA interference -- siRNA delivery; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12709
• Languages: English
• ISSNs: 1747-0277

Abstract

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. Abstract : Linear oligolysine peptides with 16 or more lysines can effectively encapsulate plasmid DNA (pDNA) into monodisperse nanoparticles for gene transfer into the cells. However, the linear oligolysine peptides are not capable of forming monodisperse complexes with siRNA, and hence, they are ineffective in siRNA delivery into cells. Because the linear peptides have limited rotation freedom, they are more suitable for cellular delivery of pDNA which has higher rotation freedom than the more physically rigid siRNA.