Chimpanzee adenovirus-mediated multiple gene therapy for age-related macular degeneration
Selena Wei-Zhang,
Bohao Cui,
Man Xing,
Jiaojiao Liu,
Yingying Guo,
Kai He,
Tinghui Bai,
Xue Dong,
Yi Lei,
Wei Zhou,
Hui Zhou,
Shengnan Liu,
Xiaohong Wang,
Dongming Zhou,
Hua Yan
Affiliations
Selena Wei-Zhang
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Bohao Cui
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China
Man Xing
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Jiaojiao Liu
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Yingying Guo
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Kai He
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China
Tinghui Bai
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Xue Dong
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China
Yi Lei
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China
Wei Zhou
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
Hui Zhou
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
Shengnan Liu
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
Xiaohong Wang
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding author
Dongming Zhou
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding author
Hua Yan
Department of Ophthalmology, Tianjin Key Laboratory of Ocular Trauma, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Laboratory of Molecular Ophthalmology, Tianjin Medical University, Tianjin 300070, China; School of Medicine, Nankai University, Tianjin, China; Corresponding author
Summary: Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr−/−) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.
