Elbadawy Hossein Mostafa, Gailledrat Marine, Desseaux Carole, Ponzin Diego, Ferrari Stefano
The Veneto Eye Bank Foundation, Via Paccagnella 11, Padiglione Giovanni Rama, Zelarino, 30174 Venice, Italy.
J Ophthalmol. 2012;2012:594869. doi: 10.1155/2012/594869. Epub 2012 Dec 26.
Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.
眼部基因治疗正迅速成为现实。截至2012年11月,约有28项临床试验获批,用于评估新型基因治疗药物。由单纯疱疹病毒1型(HSV-1)引起的病毒性感染,如疱疹性角膜炎,可导致严重并发症,甚至可能导致失明。该病很可能复发,因此角膜移植可能并非理想的治疗方案。本文将聚焦于针对疱疹性角膜炎的眼部基因治疗研究现状,包括病毒载体和非病毒载体的使用、治疗基因的递送途径、新技术以及关键研究策略。虽然纠正遗传性疾病是基因治疗领域的最初目标,但在此我们讨论转基因表达、基因替代、基因沉默或基因剪辑。筛选文献中先前报道的疱疹性角膜炎基因治疗方法,重点关注候选基因治疗靶点。讨论了常用策略,以评估使用抗病毒药物的保护性治疗与针对HSV-1长期眼部感染体征、炎症和新生血管形成的常见基因治疗的相对优势。成功的基因治疗可为疱疹性角膜炎提供创新的生理和药物解决方案。