眼部疾病的基因治疗进展

摘要

目前,全世界已有31项眼部疾病基因治疗临床试验被批准,多数仍处于研究阶段.Leber先天性黑朦(LCA)目前已开展Ⅲ期临床试验,随访时间最长6年;无脉络膜症多中心的临床试验也取得了积极效果;视网膜色素变性(RP)已开展基因治疗Ⅰ期临床试验;年龄相关性黄斑变性(AMD)基因治疗的Ⅰ期临床试验结果令人鼓舞;青光眼基因治疗中使用RNA干扰技术和优化的偶联表面活性磷脂纳米微粒也取得了良好效果.就LCA、RP、无脉络膜症、AMD和青光眼基因治疗的一些实验室及临床研究进展,包括眼部基因治疗方法、各种基因载体和常用的动物模型等进行综述.病毒载体已广泛应用于眼部疾病的基因治疗中,一些与免疫排斥和基因突变相关的潜在性风险以及个体反应的差异性促使人们去探索更安全、高效的方法.基因编辑技术的出现,必将对眼部疾病的基因治疗领域产生深远影响.%Currently,31 clinical trials have been approved,most of them are still in progress.Leber congenital amaurosis (LCA) has been conducted to phase Ⅲ clinical trials,the longest follow-up time was 6 years.A multicenter clinical trial about choroideremia has achieved positive effect.Retinitis pigmmentosa (RP) has been conducted to phase Ⅰ clinical trials.Gene therapy for phase Ⅰ clinical trials of age-related macular degeneration (AMD) have achieved encouraging results.RNA interference and optimized gemini surfactant-phospholipid nanoparticles(GL-NPs) have been applied to gene therapy for glaucoma and have achieved good effects.In this paper,laboratory and clinical research progress of gene therapy of LCA,RP,choroideremia and AMD,glaucoma are reviewed,including gene therapy drug delivery methods,gene carrier and common animal models,etc.Viral vectors have been widely used,the potential risk associated with immunogenicity and mutagenesis,the differences of individual reaction have promoted the exploration of a safer and more efficient method.Especially,the emergence of gene editing technology will bring a profound effect to gene therapy of eye disease field.