Jean Bennett

Jean Bennett, M.D., Ph.D., is the F. M. Kirby Professor of Ophthalmology (now Professor Emeritus) and Director of the Center for Advanced Retinal and Ocular Therapeutics (CAROT) at the University of Pennsylvania's Perelman School of Medicine. In 2022, she was elected a member of the National Academy of Sciences. Dr. Bennett is internationally recognized as the scientific co-founder and principal developer of Luxturna (voretigene neparvovec-rzyl)—the first FDA-approved gene therapy for use in humans. Working alongside her husband, ophthalmologist Dr. Albert M. Maguire, Bennett first envisioned using genetic medicine to treat retinal blindness in the mid-1980s. Following initial animal tests in 2000 and the first human trials in 2007, Luxturna received historic FDA approval in December 2017 for treating Leber congenital amaurosis (LCA) and retinitis pigmentosa caused by biallelic RPE65 mutations. Bennett's landmark 2001 Nature Genetics publication demonstrated that AAV-mediated RPE65 gene therapy could restore vision in RPE65-deficient Briard dogs—a large animal model of childhood blindness. This proof-of-concept study directly catalyzed human clinical translation. In 2008, Bennett and Maguire reported the first human RPE65 gene therapy clinical trial in The New England Journal of Medicine, demonstrating safety and efficacy in three LCA patients following subretinal injection of AAV2-RPE65. Subsequent phase I dose-escalation trials revealed age-dependent treatment effects, with pediatric patients achieving the greatest improvements—all children gained ambulatory vision—supporting early intervention for optimal therapeutic benefit. Luxturna delivers a normal copy of the RPE65 gene via a single subretinal injection using AAV2 vectors, restoring production of proteins that enable light receptors to function in the retina. Phase III clinical trials involving 41 patients (ages 4-44 years) demonstrated significant improvements in navigating obstacle courses under low-light conditions. Bennett's laboratory at CAROT continues developing gene therapies for inherited retinal diseases including autosomal recessive Stargardt disease and choroideremia, collaborating with partners such as Gyroscope Therapeutics. Her work established the complete translational pathway from basic research through animal models to clinical application, inaugurating the clinical era of AAV gene therapy.

Jean Bennett医学博士、哲学博士，是宾夕法尼亚大学佩雷尔曼医学院F. M. Kirby眼科学教授（现为荣誉退休教授）和视网膜与眼部高级治疗中心（CAROT）主任。2022年，她当选为美国国家科学院院士。 Bennett博士国际公认为Luxturna (voretigene neparvovec-rzyl)的科学共同创始人和主要开发者——首个FDA批准用于人类的基因治疗。与她的丈夫、眼科医生Albert M. Maguire博士一起工作，Bennett在1980年代中期首次设想使用基因药物治疗视网膜失明。经过2000年的初步动物测试和2007年的首次人体试验，Luxturna于2017年12月获得FDA历史性批准，用于治疗由双等位基因RPE65突变引起的Leber先天性黑蒙症(LCA)和视网膜色素变性。 Bennett 2001年发表在Nature Genetics的里程碑论文证明AAV介导的RPE65基因治疗可以恢复RPE65缺陷Briard犬的视力——儿童失明的大型动物模型。这项概念验证研究直接催化了人类临床转化。2008年，Bennett和Maguire在《新英格兰医学杂志》报道了首个人类RPE65基因治疗临床试验，证明了三名LCA患者在视网膜下注射AAV2-RPE65后的安全性和有效性。随后的I期剂量递增试验揭示了年龄依赖性治疗效果，儿科患者取得了最大改善——所有儿童都获得了行走视力——支持早期干预以获得最佳治疗效果。 Luxturna通过使用AAV2载体进行单次视网膜下注射递送正常的RPE65基因副本，恢复使视网膜中的光感受器能够正常工作的蛋白质生产。III期临床试验涉及41名患者（4-44岁），证明在低光条件下导航障碍物课程能力显著改善。 Bennett在CAROT的实验室继续开发遗传性视网膜疾病的基因治疗，包括常染色体隐性Stargardt病和脉络膜缺失，与Gyroscope Therapeutics等合作伙伴合作。她的工作建立了从基础研究通过动物模型到临床应用的完整转化途径，开创了AAV基因治疗的临床时代。