Polyethylenimine-based non-viral gene delivery systems
Polyethylenimine-based non-viral gene delivery systems
复制标题
DOI：
10.1016/j.ejpb.2004.11.011
复制
发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Göpferich, A
中科院分区：
文献类型：
--
作者：
Lungwitz, U;Breunig, M;Göpferich, A
基因治疗已成为治疗许多目前被认为无法治愈的遗传性或获得性疾病的一种有前途的策略。与病毒载体相比，非病毒载体具有制备简单、稳定性好、易于修饰和相对安全等优点，引起了人们的极大兴趣。不幸的是，它们也遭受较低的转染效率，需要额外的努力来优化它们。阳离子聚合物聚乙烯亚胺（PEI）已被广泛用于体外和体内非病毒转染，并且与其他聚阳离子相比具有优势，因为它结合了强的DNA压缩能力和内在的内体溶解活性。在这里，我们深入了解基于PEI的非病毒载体克服细胞内障碍的策略，包括改进复合物制备方法和掺入内体溶解剂或核定位信号。近年来，基于PEI的非病毒载体已被局部或全身递送，主要是将基因递送靶向肿瘤组织、肺或肝。这需要有效地屏蔽转染复合物以防止与血液组分、细胞外基质和非靶向细胞的非特异性相互作用以及靶向部分的附着的策略，这允许定向基因递送至所需的细胞或组织。在这种情况下，材料，促进新的基于PEI的非病毒载体的设计进行了描述。(c)2005 Elsevier B.V.保留所有权利。
Gene therapy has become a promising strategy for the treatment of many inheritable or acquired diseases that are currently considered incurable. Non-viral vectors have attracted great interest, as they are simple to prepare, rather stable, easy to modify and relatively safe, compared to viral vectors. Unfortunately, they also suffer from a lower transfection efficiency, requiring additional effort for their optimization. The cationic polymer polyethylenimine (PEI) has been widely used for non-viral transfection in vitro and in vivo and has an advantage over other polycations in that it combines strong DNA compaction capacity with an intrinsic endosomolytic activity. Here, we dive some insight into strategies developed for PEI-based non-viral vectors to overcome intracellular obstacles, including the improvement of methods for polyplex preparation and the incorporation of endosomolytic agents or nuclear localization signals. In recent years, PEI-based non-viral vectors have been locally or systemically delivered, mostly to target gene delivery to tumor tissue, the lung or liver. This requires strategies to efficiently shield transfection polyplexes against non-specific interaction with blood components, extracellular matrix and untargeted cells and the attachment of targeting moieties, which allow for the directed gene delivery to the desired cell or tissue. In this context, materials, facilitating the design of novel PEI-based non-viral vectors are described. (c) 2005 Elsevier B.V. All rights reserved.