非病毒载体在遗传性视网膜变性基因治疗中的应用

Non-viral vector for gene therapy in inherited retinal degeneration

遗传性视网膜变性(IRD)发病机制复杂多样,常常导致不可逆盲,目前尚缺乏有效的治疗方法。近年来,针对IRD的基因治疗显示出广阔的应用前景,而如何将基因药物递送至靶细胞并安全、高效地表达成为目前研究发展的关键点。病毒载体系统转染效率较高,但具有潜在的免疫反应和生物安全等问题,其临床应用的局限性使非病毒载体系统的开发应运而生。DNA纳米复合体是新型非病毒载体的研究热点之一,这种聚合物/DNA复合物纳米粒子由多肽、脂质、多糖等物质压缩和包裹DNA而成,在IRD的应用上取得了较大的进展。此外,非病毒载体在成本、制备难易度、包装容量及安全性上均显示出其优势,为视网膜色素变性、Stargardt病、先天性视网膜劈裂、Leber先天性黑矇等IRD的基因治疗提供了新的研究思路。本文对近年来非病毒载体系统在转染效率、靶向性和安全性等方面的进展及其在IRD基因治疗中的应用进行综述。

Inherited retinal degeneration(IRD),a group of diseases often causing irreversible blindness,with multiple pathogenesis,still lacks effective treatments currently.Development of effective therapeutics is a primary research goal.Despite rapid advances in gene therapy during the past decades,the most challenging aspect of gene therapy in clinical applications for IRD is to deliver the curative molecules to achieve optimal expression levels in target cells safely.Apart from high gene transfection efficiency,there are still many limitations,such as immunogenicity,biosafety issue,etc.in the application of viral vectors,which drive the development of gene therapy based on non-viral vectors.As one of the hot research topics in non-viral vectors,encouraging progress has been made in DNA nanoparticles for IRD treatment.The polymer/DNA complex nanoparticle is compacted and encapsulated DNA via peptides,lipids,or polysaccharides.Besides,the non-viral delivery system shows cost,preparation,packaging capacity,and safety advantages,providing a promising non-viral platform for safe and effective treatment of IRD,such as retinitis pigmentosa,Stargardt disease,X-linked juvenile retinoschisis,Leber congenital amaurosis,and so on.In this article,advances in transfection efficiency,targeting ability and safety of non-viral gene therapy and its application in IRD were reviewed.