Department of Haematology, UCL-Cancer Institute, London, United Kingdom.
Katharine Dormandy Haemophilia and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom.
Hum Gene Ther. 2022 Sep;33(17-18):879-888. doi: 10.1089/hum.2022.169.
Gene therapy is an exciting therapeutic concept that offers the promise of a cure for an array of inherited and acquired disorders. The liver has always been a key target for gene therapy as it controls essential biological processes including digestion, metabolism, detoxification, immunity, and blood coagulation. Metabolic disorders of hepatic origin number several hundreds, and for many, liver transplantation remains the only cure. Liver-targeted gene therapy is an attractive treatment modality for many of these conditions. After years of failure, substantial progress in this field in the past decade has resulted in promising clinical efficacy and safety in patients with monogenetic disorders with Valoctocogene roxaparvovec (Roctavian), the first gene therapy for treatment for hemophilia A, to be approved in Europe. Another, Etranacogene dezaparvovec (AMT-061) for hemophilia B is also in the final stages of approval. A number of other liver targeted gene therapy products are at an advanced stage of development, thus heralding a new era of potentially curative molecular medicine. This review explores the recent clinical advances in liver targeted gene therapy as well as the challenges that need to be overcome for the widespread adoption of this new treatment paradigm.
基因治疗是一种令人兴奋的治疗概念，为一系列遗传性和获得性疾病提供了治愈的可能。肝脏一直是基因治疗的主要靶点，因为它控制着包括消化、代谢、解毒、免疫和血液凝固在内的重要生物过程。源自肝脏的代谢紊乱有数百种之多，对于许多疾病来说，肝移植仍然是唯一的治疗方法。对于许多这些疾病，肝脏靶向基因治疗是一种有吸引力的治疗方式。经过多年的失败，过去十年中该领域的实质性进展使得 Valoctocogene roxaparvovec（Roctavian）治疗 A 型血友病的基因治疗方法在欧洲获得批准，为单基因疾病患者带来了有希望的临床疗效和安全性。另一种用于治疗 B 型血友病的 Etranacogene dezaparvovec（AMT-061）也已进入批准的最后阶段。许多其他肝脏靶向基因治疗产品也处于开发的高级阶段，因此预示着一个潜在的治愈性分子医学新时代的到来。本文探讨了肝脏靶向基因治疗的最新临床进展，以及为广泛采用这种新的治疗模式需要克服的挑战。
