尽管该领域在过去三十年里经历了起起落落，但基因治疗科学仍在不断发展，并为越来越多的疾病提供持久的治疗方法。针对不同器官系统的各种遗传性和获得性疾病正在进行积极的临床试验。方法包括对血液干细胞 (HSC)、T 淋巴细胞和其他免疫细胞进行体外修饰，以及通过局部或全身给药将基因或基因编辑试剂体内递送至相关靶细胞。在本文中，我们重点介绍基因治疗三个高度活跃领域的成功和持续挑战：针对造血干细胞的遗传性血细胞疾病、使用嵌合抗原受体基因修饰的免疫效应细胞的恶性疾病，以及眼科、神经科和凝血科使用腺相关病毒（AAV）载体体内施用来治疗疾病。近年来，许多此类疾病已经有了真正的治愈方法，其持续的临床效益超过了其他医疗方法。这些治疗方法中的每一种都面临着持续的挑战，即一次性成本高昂，以及按照药理学质量和一致性标准制造治疗剂（生物病毒和细胞产品）的复杂性。需要新的报销模式，以使这些创新治疗方法广泛为有需要的患者提供。© 2023。作者。

Despite the ups and downs in the field over three decades, the science of gene therapy has continued to advance and provide enduring treatments for increasing number of diseases. There are active clinical trials approaching a variety of inherited and acquired disorders of different organ systems. Approaches include ex vivo modification of hematologic stem cells (HSC), T lymphocytes and other immune cells, as well as in vivo delivery of genes or gene editing reagents to the relevant target cells by either local or systemic administration. In this article, we highlight success and ongoing challenges in three areas of high activity in gene therapy: inherited blood cell diseases by targeting hematopoietic stem cells, malignant disorders using immune effector cells genetically modified with chimeric antigen receptors, and ophthalmologic, neurologic, and coagulation disorders using in vivo administration of adeno-associated virus (AAV) vectors. In recent years, there have been true cures for many of these diseases, with sustained clinical benefit that exceed those from other medical approaches. Each of these treatments faces ongoing challenges, namely their high one-time costs and the complexity of manufacturing the therapeutic agents, which are biological viruses and cell products, at pharmacologic standards of quality and consistency. New models of reimbursement are needed to make these innovative treatments widely available to patients in need.© 2023. The Author(s).