Lungwitz U, Breunig M, Blunk T, Göpferich A
Department of Pharmacy and Chemistry, Pharmaceutical Technology Unit, University of Regensburg, Regensburg, Germany.
Eur J Pharm Biopharm. 2005 Jul;60(2):247-66. doi: 10.1016/j.ejpb.2004.11.011.
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 give 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.
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景的策略。与病毒载体相比，非病毒载体因其制备简单、相对稳定、易于修饰且相对安全而备受关注。不幸的是，它们的转染效率也较低，需要额外努力对其进行优化。阳离子聚合物聚乙烯亚胺（PEI）已在体外和体内广泛用于非病毒转染，与其他聚阳离子相比具有优势，即它将强大的DNA压缩能力与内在的溶酶体溶解活性结合在一起。在此，我们深入探讨了为基于PEI的非病毒载体开发的克服细胞内障碍的策略，包括改进多聚体的制备方法以及引入溶酶体溶解剂或核定位信号。近年来，基于PEI的非病毒载体已通过局部或全身给药，主要用于将基因靶向递送至肿瘤组织、肺或肝脏。这需要采取策略来有效保护转染多聚体免受与血液成分、细胞外基质和非靶向细胞的非特异性相互作用，并连接靶向部分，从而实现将基因定向递送至所需的细胞或组织。在这种情况下, 描述了有助于设计新型基于PEI的非病毒载体的材料。
