Abstract：
Throughout the years, several hundred million people with rare genetic disorders have been receiving only symptom management therapy. However, research and development efforts worldwide have led to the development of long-lasting, highly efficient, and safe gene therapy for a wide range of hereditary diseases. Improved viral vectors are now able to evade the preexisting immunity and more efficiently target and transduce therapeutically relevant cells, ensuring genome maintenance and expression of transgenes at the relevant levels. Hematological, ophthalmological, neurodegenerative, and metabolic therapeutic areas have witnessed successful treatment of hemophilia and muscular dystrophy, restoration of immune system in children with immunodeficiencies, and restoration of vision. This review focuses on three leading vector platforms of the past two decades: adeno-associated viruses (AAVs), adenoviruses (AdVs), and lentiviruses (LVs). Special attention is given to successful preclinical and clinical studies that have led to the approval of gene therapies: six AAV-based (Glybera® for lipoprotein lipase deficiency, Luxturna® for retinal dystrophy, Zolgensma® for spinal muscular atrophy, Upstaza® for AADC, Roctavian® for hemophilia A, and Hemgenix® for hemophilia B) and three LV-based (Libmeldy® for infantile metachromatic leukodystrophy, Zynteglo® for β-thalassemia, and Skysona® for ALD). The review also discusses the problems that arise in the development of gene therapy treatments, which, nevertheless, do not overshadow the successes of already developed gene therapies and the hope these treatments give to long-suffering patients and their families.
摘要：
多年来,数亿患有罕见遗传病的人一直只接受症状管理治疗。然而,世界各地的研究和开发努力导致了持久的发展，高效,以及广泛的遗传性疾病的安全基因疗法。改进的病毒载体现在能够逃避预先存在的免疫，更有效地靶向和转导治疗相关的细胞，确保基因组维持和转基因在相关水平上的表达。血液学,眼科,神经退行性疾病，和代谢治疗领域见证了血友病和肌营养不良的成功治疗，免疫缺陷儿童免疫系统的恢复，恢复视力。这篇综述集中在过去二十年中的三个主要载体平台：腺相关病毒（AAV），腺病毒（AdVs），和慢病毒(LV)。特别注意成功的临床前和临床研究，导致基因疗法的批准：六个基于AAV的（Glybera®用于脂蛋白脂肪酶缺乏症，Luxturna®治疗视网膜营养不良，Zolgensma®治疗脊髓性肌萎缩症，用于AADC的Upstaza®,Roctavian®治疗A型血友病，和Hemgenix®用于血友病B）和三个基于LV的（Libmeldy®用于婴儿变色性脑白质营养不良，Zynteglo®用于β-地中海贫血，和Skysona®用于ALD)。该综述还讨论了基因治疗治疗发展中出现的问题，which,然而，不要掩盖已经开发的基因疗法的成功，以及这些疗法给长期受苦的患者及其家人带来的希望。
