Inherited genetic disorders are progressive in nature and lead to organ dysfunction or death in severe cases. At present, there are no permanent treatment options for >95% of inherited disorders. Different modes of inheritance, type of gene(s) involved, and population-based variations add further complexity to finding suitable cures for approximately 400 million patients worldwide. Gene therapy is a very promising molecular technique for the treatment of rare genetic disorders. Gene therapy functions on the basis of restoration, replacement, inhibition, and, most recently, editing of gene(s) to rescue the disease phenotype. Recent reports show that increasing numbers of gene therapy clinical trials are using viral vectors (64.2%) when compared with non-viral vectors. Rapid development of efficient viral vector systems like the adeno-associated virus (AAV) and lentivirus has significantly contributed to this progress. Notably, AAV-mediated gene therapy has shown high potential for genetic disease treatment as evident from recent clinical trials for the eye (NCT00999609), blood (NCT00979238), and neuro-muscular systems (NCT02122952). Safety and efficacy are the two most critical features required for vector(s) to qualify for pre-clinical and clinical trial approval. The process of clinical-grade vector production, evaluation, and approvals for gene therapy products requires significant technological development, knowledge enhancement, and large financial investments. Additionally, trained manpower is required to meet the demands for constant technical innovation. These factors together contribute towards exorbitant prices for every dose of a gene therapy product and thus pose a challenge for the gene therapy field. The Indian subcontinent has traditionally lagged behind North America, Europe, Japan, and others in gene therapy clinical trials due to factors like inadequate industrial-scientific infrastructure, lack of accessible and organized patient databases, low financial investments, etc. However, over the last decade, increasing awareness of rare diseases, and international approvals of gene therapies such as Luxturna, Zolgensma, Hemgenix, etc., have spurred gene therapy development in India as well. In view of these advances, this article outlines gene therapy research, regulatory processes, and the launch of gene therapy clinical trials in India in the context of major developments worldwide. We briefly describe ongoing gene therapy research across Indian organizations and the nascent gene therapy product manufacturing. Further, we highlight the various initiatives from the medical and patient community to avail rehabilitation and gene therapy options. We briefly discuss the roles of regulatory agencies and guidelines for gene therapy clinical trials in India. We anticipate that this concise review will highlight the promise of gene therapy for the large population of rare disease patients in India.

遗传性遗传疾病本质上是进行性的，严重时会导致器官功能障碍或死亡。目前，>95% 的遗传性疾病没有永久性的治疗方案。不同的遗传模式、所涉及的基因类型以及基于人群的变异进一步增加了为全球约 4 亿患者寻找合适治疗方法的复杂性。基因疗法是治疗罕见遗传性疾病的一种非常有前途的分子技术。基因治疗的作用基于恢复、替代、抑制以及最近的基因编辑以挽救疾病表型。最近的报告显示，与非病毒载体相比，越来越多的基因治疗临床试验使用病毒载体（64.2%）。腺相关病毒（AAV）和慢病毒等高效病毒载体系统的快速发展为这一进展做出了重大贡献。值得注意的是，AAV 介导的基因疗法在遗传疾病治疗方面显示出巨大的潜力，这一点从最近的眼部 (NCT00999609)、血液 (NCT00979238) 和神经肌肉系统 (NCT02122952) 临床试验中可以看出。安全性和有效性是载体获得临床前和临床试验批准所需​​的两个最关键的特征。基因治疗产品的临床级载体生产、评估和批准过程需要大量的技术开发、知识增强和大量的财务投资。此外，还需要训练有素的人力来满足不断技术创新的需求。这些因素共同导致每剂基因治疗产品的价格过高，从而对基因治疗领域提出了挑战。由于工业科学基础设施不足、缺乏可访问且有组织的患者数据库、金融投资较低等因素，印度次大陆在基因治疗临床试验方面历来落后于北美、欧洲、日本和其他国家。十年来，人们对罕见疾病的认识不断提高，以及 Luxturna、Zolgensma、Hemgenix 等基因疗法在国际上获得批准，也刺激了印度基因疗法的发展。鉴于这些进展，本文概述了基因治疗研究、监管流程以及在全球重大发展背景下在印度启动的基因治疗临床试验。我们简要描述了印度各组织正在进行的基因治疗研究和新兴的基因治疗产品制造。此外，我们还重点介绍了医疗界和患者界为利用康复和基因治疗方案而采取的各种举措。我们简要讨论印度基因治疗临床试验监管机构的作用和指南。我们预计这篇简明的综述将凸显基因治疗对印度大量罕见病患者的前景。