An engineered intravitreal injection RPE-tropic AAV vector expressing a bispecific antibody binding VEGF-A and ANG-2 rescues nAMD in animal models and …
Brief intro:
- Author: Yuan Cai, Yonghao Gu, Jie Zhang, Ying Zhu, Zhen Ma, Qin He,Yongjia Sun, Mengmeng Yuan, Xiaojun Li, Kai Zhu, Bolong Miao, Jin Zhao, Juan Liu, Min Tang, Dali Tong, Lixia Feng, Ming Ma, Guisheng Zhong, Zilong Qiu, Tian Xue
- Journal: Research
- Doi: https://www.doi.org/10.34133/research.0717
- Publication Date: 2025 May 8
Abstract
Anti-angiogenesis gene therapy based on adeno-associated virus (AAV) vectors represents a promising advancement in the treatment of neovascular age-related macular degeneration (nAMD), providing an alternative to antibody-based therapies. However, the development of a safe and effective AAV vector capable of precisely targeting neovascularization and choroidal leakage remains a critical unmet need. In the present study, we engineered a novel intravitreal (IVT)-administered AAV vector with retinal pigment epithelium (RPE)-specific tropism. This vector demonstrated robust and localized gene expression in RPE cells while maintaining a favorable safety profile. The RPE-tropic AAV vector delivered a dual-acting antibody against vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG-2), exhibited strong therapeutic efficacy and tolerability in both rodent and non-human primate choroidal neovascularization (CNV) models. Based on the promising pre-clinical data, a singlecenter, single-arm, investigator-initiated trial (ChiCTR2400085329) was conducted to assess its safety and efficacy in patients with nAMD. The RPE-tropic AAV vector expressing anti-VEGF-A and anti-ANG-2 effectively alleviated disease progression and was well tolerated in the clinical setting. These findings highlight the potential of this engineered AAV-RPE capsid as a versatile platform for gene therapy, not only for nAMD but also for other ocular diseases involving RPE cells.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
