iScience (Oct 2023)

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

Journal volume & issue
Vol. 26, no. 10
p. 107939

Abstract

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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.

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