Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA.
Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA.
复制标题
DOI：
10.1111/cbdd.12709
复制
发表时间：
2016-05
影响因子：
3
通讯作者：
Tagalakis AD
中科院分区：
文献类型：
--
作者：
Kwok A;McCarthy D;Hart SL;Tagalakis AD
采用4种具有8 （K8）、16 （K16）、24 （K24）和32 （K32）赖氨酸的线性低聚赖氨酸肽，研究了赖氨酸肽长度对DNA和siRNA包装传递的影响。含有16个赖氨酸或更长赖氨酸的寡聚赖氨酸肽可稳定地形成单分散颗粒，并具有最佳的质粒DNA （pDNA）转染效率，但K8制剂在阴离子肝素挑战下稳定性较差，因此转染效率较低。然而，在这里我们发现低聚赖氨酸不能包装siRNA形成稳定的复合物，因此siRNA转染不成功。这些结果表明，阳离子肽的物理结构和长度及其电荷比是pDNA和siRNA稳定颗粒形成的关键参数，没有包装，传递和转染是无法实现的。
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.