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

被引：27

作者：

Kwok, Albert ^{[1
,3
]}

McCarthy, David ^{[2
]}

Hart, Stephen L. ^{[1
]}

Tagalakis, Aristides D. ^{[1
]}

机构：

[1] UCL, UCL Inst Child Hlth, Expt & Personalised Med Sect, 30 Guilford St, London WC1N 1EH, England

[2] UCL Sch Pharm, 29-39 Brunswick Sq, London WC1N 1AX, England

[3] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Box 289, Cambridge CB2 0QQ, England

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2016年 / 87卷 / 05期

基金：

英国工程与自然科学研究理事会;

关键词：

biophysical characteristics; DNA delivery; gene therapy; oligolysine peptide; RNA interference; siRNA delivery; GENE-TRANSFER COMPLEXES; POLY-L-LYSINE; IN-VITRO; POLYELECTROLYTE COMPLEXES; TARGETED NANOCOMPLEXES; MOLECULAR-WEIGHT; CELLULAR UPTAKE; HK PEPTIDES; DELIVERY; TRANSFECTION;

D O I：

10.1111/cbdd.12709

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：747 / 763

页数：17

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