Institute of Biophysics and Cell Engineering of NASB , Minsk , Belarus.
Expert Opin Drug Deliv. 2013 Dec;10(12):1687-98. doi: 10.1517/17425247.2013.853661. Epub 2013 Oct 30.
Gene therapy is one of the most effective ways to treat major infectious diseases, cancer and genetic disorders. It is based on several viral and non-viral systems for nucleic acid delivery. The number of clinical trials based on application of non-viral drug and gene delivery systems is rapidly increasing.
This review discusses and summarizes recent advances in poly(amidoamine) dendrimers as effective gene carriers in vitro and in vivo, and their advantages and disadvantages relative to viral vectors and other non-viral systems (liposomes, linear polymers) are considered.
In this regard, dendrimers are non-immunogenic and have the highest efficiency of transfection among other non-viral systems, and none of the drawbacks characteristic for viral systems. The toxicity of dendrimers both in vitro and in vivo is an important question that has been addressed on many occasions. Several non-toxic and efficient multifunctional dendrimer-based conjugates for gene delivery, along with modifications to improve transfection efficiency while decreasing cytotoxicity, are discussed. Twelve paradigms that affected the development of dendrimer-based gene delivery are described. The conclusion is that dendrimers are promising candidates for gene delivery, but this is just the beginning and further studies are required before using them in human gene therapy.
基因治疗是治疗重大传染病、癌症和遗传疾病最有效的方法之一。它基于几种用于核酸递送的病毒和非病毒系统。基于非病毒药物和基因递送系统应用的临床试验数量正在迅速增加。
本文讨论并总结了多聚（酰胺-胺）树枝状大分子作为有效基因载体在体外和体内的最新进展，并考虑了它们相对于病毒载体和其他非病毒系统（脂质体、线性聚合物）的优缺点。
在这方面，树枝状大分子具有非免疫原性，在其他非病毒系统中具有最高的转染效率，并且没有病毒系统的任何缺点。树枝状大分子在体外和体内的毒性是一个重要的问题，已经多次得到解决。本文讨论了几种用于基因递送的无毒且高效的多功能树枝状大分子缀合物，以及为了提高转染效率同时降低细胞毒性而进行的修饰。描述了影响基于树枝状大分子的基因递送发展的 12 个范例。结论是，树枝状大分子是基因递送的有前途的候选物，但这仅仅是个开始，在将其用于人类基因治疗之前还需要进一步研究。
