Solinís M Ángeles, del Pozo-Rodríguez Ana, Apaolaza Paola S, Rodríguez-Gascón Alicia
Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
Eur J Pharm Biopharm. 2015 Sep;95(Pt B):331-42. doi: 10.1016/j.ejpb.2014.12.022. Epub 2014 Dec 20.
Gene therapy to treat ocular disorders is still starting, and current therapies are primarily experimental, with most human clinical trials still in research state, although beginning to show encouraging results. Currently 33 clinical trials have been approved, are in progress, or have been completed. The most promising results have been obtained in clinical trials of ocular gene therapy for Leber Congenital Amaurosis, which have prompted the study of several ocular diseases that are good candidates to be treated with gene therapy: glaucoma, age-related macular degeneration, retinitis pigmentosa, or choroideremia. The success of gene therapy relies on the efficient delivery of the genetic material to target cells, achieving optimum long-term gene expression. Although viral vectors have been widely used, their potential risk associated mainly with immunogenicity and mutagenesis has promoted the design of non-viral vectors. In this review, the main administration routes and the most studied delivery systems, viral and non-viral, for ocular gene therapy are presented. The primary ocular disease candidates to be treated with gene therapy have been also reviewed, including the genetic basis and the most relevant preclinical and clinical studies.
用于治疗眼部疾病的基因疗法仍处于起步阶段，目前的疗法主要是实验性的，尽管已开始显示出令人鼓舞的结果，但大多数人体临床试验仍处于研究状态。目前已有33项临床试验获得批准、正在进行或已经完成。在针对莱伯先天性黑蒙的眼部基因治疗临床试验中取得了最有希望的结果，这促使人们对几种有望通过基因疗法治疗的眼部疾病进行研究：青光眼、年龄相关性黄斑变性、视网膜色素变性或脉络膜视网膜病变。基因治疗的成功依赖于将遗传物质有效递送至靶细胞，实现最佳的长期基因表达。尽管病毒载体已被广泛使用，但其主要与免疫原性和诱变相关的潜在风险促使了非病毒载体的设计。在这篇综述中，介绍了眼部基因治疗的主要给药途径以及研究最多的病毒和非病毒递送系统。还综述了有望通过基因疗法治疗的主要眼部疾病候选者，包括其遗传基础以及最相关的临床前和临床研究。
