Geng Guannan, Xu Yixin, Hu Ziying, Wang Hui, Chen Xiaoyun, Yuan Wei, Shu Yilai
ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; MOE Engineering Research Center of Gene Technology, China.
Chongqing General Hospital (The Affiliated Hospital of Chongqing University), Chongqing, China.
EBioMedicine. 2025 Jul 1;118:105834. doi: 10.1016/j.ebiom.2025.105834.
Advancements in gene therapy have achieved significant milestones in treating human diseases, offering renewed hope to patients with limited options. Key to this progress are vectors, which include both viral and non-viral methodologies that impact the success of gene therapy. Over the past two decades, three widely used viral vectors-lentiviruses (LV), adenoviruses (Ad), and adeno-associated viruses (AAV)-have enabled notable preclinical and clinical successes, including the approval of Luxturna for a genetic retinal disease and CAR-T therapies for blood cancers. Recently, the first-in-human dual AAV therapy for hereditary hearing loss, which overcomes large gene delivery, has showcased the restoration of auditory function for patients. Additionally, non-viral vectors such as lipid nanoparticles (LNP) and N-acetylgalactosamine (GalNAc) have led to successful gene therapy products. This review focuses on both viral and non-viral delivery systems in gene therapy, highlighting their current state and future perspectives in treating human diseases.
基因治疗的进展在治疗人类疾病方面取得了重大里程碑，为选择有限的患者带来了新的希望。这一进展的关键是载体，其中包括影响基因治疗成功的病毒和非病毒方法。在过去二十年中，三种广泛使用的病毒载体——慢病毒（LV）、腺病毒（Ad）和腺相关病毒（AAV）——取得了显著的临床前和临床成功，包括Luxturna获批用于治疗遗传性视网膜疾病以及CAR-T疗法用于治疗血癌。最近，用于遗传性听力损失的首例人体双AAV疗法克服了大基因递送难题，展示了对患者听觉功能的恢复。此外，脂质纳米颗粒（LNP）和N-乙酰半乳糖胺（GalNAc）等非病毒载体也带来了成功的基因治疗产品。本综述重点关注基因治疗中的病毒和非病毒递送系统，突出它们在治疗人类疾病方面的现状和未来前景。
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