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Abstract：
Gene therapy has now evolved as the upcoming modality for management of many disorders, both inheritable and non-inheritable. Knowledge of genetics pertaining to a disease has therefore become paramount for physicians across most specialities. Inheritable retinal dystrophies (IRDs) are notorious for progressive and relentless vision loss, frequently culminating in complete blindness in both eyes. Leber\'s congenital amaurosis (LCA) is a typical example of an IRD that manifests very early in childhood. Research in gene therapy has led to the development and approval of voretigene neparvovec (VN) for use in patients of LCA with a deficient biallelic RPE65 gene. The procedure involves delivery of a recombinant virus vector that carries the RPE65 gene in the subretinal space. This comprehensive review reports the evidence thus far in support of gene therapy for LCA. We explore and compare the various gene targets including but not limited to RPE65, and discuss the choice of vector and method for ocular delivery. The review details the evolution of gene therapy with VN in a phased manner, concluding with the challenges that lie ahead for its translation for use in communities that differ much both genetically and economically.
摘要：
基因治疗现在已经发展成为许多疾病的管理方式，可继承和不可继承。因此，对于大多数专业的医生来说，与疾病有关的遗传学知识已变得至关重要。遗传性视网膜营养不良（IRD）因进行性和无情的视力丧失而臭名昭著，经常导致双眼完全失明。Leber的先天性黑蒙（LCA）是IRD的典型例子，在儿童早期就表现出来。基因治疗的研究已导致开发并批准了voreticeneneparvovec（VN），用于双等位基因RPE65基因缺陷的LCA患者。该方法涉及在视网膜下间隙中递送携带RPE65基因的重组病毒载体。这篇全面的综述报道了迄今为止支持LCA基因治疗的证据。我们探索和比较了各种基因靶标，包括但不限于RPE65，并讨论了载体和眼部递送方法的选择。该综述以分阶段的方式详细介绍了VN基因治疗的发展。总结其在基因和经济上差异很大的社区中使用的翻译面临的挑战。
