Wang Kai, Huang Qian, Qiu Fuming, Sui Meihua
Center for Cancer Biology and Innovative Therapeutics, Zhejiang Provincial People's Hospital, Hangzhou, China.
Curr Med Chem. 2015;22(35):4118-36. doi: 10.2174/0929867322666151001121601.
A key barrier to the development of gene therapy remains the lack of safe, efficient and easily controllable vehicles for gene delivery. The fundamental problems associated with the viral vehicles, e.g. lack of specificity and immunogenic potential, have driven the development of non-viral systems of gene delivery. In the last decade, studies on p53 gene replacement therapy have dominated the literature. Although clinical trials of p53 gene therapy have achieved limited success, it remains the only tumor suppressor gene to be evaluated formally in clinical trials for cancer treatment, with increasing focus on delivery using non-viral systems. In this article, we particularly review current investigations on p53 gene delivery using non-viral methods, including both physical and chemical approaches, with an emphasis on the latter. The existing opportunities and challenges for successful p53 cancer gene therapy are also discussed.
基因治疗发展的一个关键障碍仍然是缺乏安全、高效且易于控制的基因递送载体。与病毒载体相关的基本问题,例如缺乏特异性和免疫原性潜力,推动了非病毒基因递送系统的发展。在过去十年中,关于p53基因替代疗法的研究在文献中占据主导地位。尽管p53基因治疗的临床试验取得了有限的成功,但它仍然是唯一在癌症治疗临床试验中接受正式评估的肿瘤抑制基因,并且越来越关注使用非病毒系统进行递送。在本文中,我们特别回顾了目前使用非病毒方法进行p53基因递送的研究,包括物理和化学方法,重点是后者。还讨论了成功进行p53癌症基因治疗的现有机遇和挑战。