Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA; Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea; Center for Food and Bioconvergence & World Class University Biomodulation Major, Seoul National University, Seoul 151-742, South Korea.
Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
J Control Release. 2014 Nov 10;193:74-89. doi: 10.1016/j.jconrel.2014.05.055. Epub 2014 Jun 3.
Non-viral gene delivery systems are one of the most potential alternatives to viral vectors because of their less immunogenicity, less toxicity and easy productivity in spite of their low capacity of gene transfection using DNA or silencing using siRNA compared to that of viral vectors. Among non-viral systems, the polycationic derivatives are the most popular gene carriers since they can effectively condense nucleic acids to transfer into the cells, especially the polyethylenimine (PEI) which has been used as a golden standard polymer owing to its high buffering ability for endosomal escape of gene to be expressed. However, PEI has severe problems for its toxicity due to the high positive charge density and non-degradability although the toxicity of PEI depends on its molecular weight (MW) and structure. Therefore, a considerable attention has been paid on synthesis of degradable PEI derivatives using low MW one because low MW PEI is much less toxic than high MW PEI. Other degradable polycationic gene carriers such as polyamidoamines (PAA) and cyclodextrin (CD)-based polycations are also in a significant interest because of their high transfection efficiency with low toxicity. This review in detail explains the recent developments on these three major degradable polycations as promising carriers for deoxyribonucleic acid (DNA) and small interfering RNA (siRNA).
非病毒基因传递系统是最有潜力的病毒载体替代品之一,因为它们的免疫原性较低,毒性较小,并且易于生产,尽管与病毒载体相比,它们使用 DNA 进行基因转染的能力较低,使用 siRNA 进行沉默的能力也较低。在非病毒系统中,阳离子聚合物衍生物是最受欢迎的基因载体,因为它们可以有效地将核酸凝聚并转入细胞内,特别是聚亚乙基亚胺(PEI),由于其具有高缓冲能力,可使内体逃逸的基因得以表达,因此被用作金标准聚合物。然而,由于正电荷密度高且不可降解,PEI 存在严重的毒性问题,尽管 PEI 的毒性取决于其分子量(MW)和结构。因此,人们相当关注使用低 MW 的可降解 PEI 衍生物的合成,因为低 MW 的 PEI 比高 MW 的 PEI 毒性小得多。其他可降解阳离子基因载体,如聚酰胺胺(PAA)和基于环糊精(CD)的聚阳离子,由于其具有低毒性和高转染效率,也受到了极大的关注。本文详细介绍了这三种主要的可降解聚阳离子作为脱氧核糖核酸(DNA)和小干扰 RNA(siRNA)的有前途的载体的最新进展。