Gene therapy for age-related macular degeneration

Nicholas A. Moore, Peter Bracha, Rehan M. Hussain, Nuria Morral, Thomas A. Ciulla

Research output: Contribution to journalReview article

21 Scopus citations


Introduction: In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with ‘real world’ undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD. Subsequently, gene therapy for AMD shifted to the investigation of soluble fms-like tyrosine kinase-1 (sFLT-1), an endogenously expressed VEGF inhibitor, binding and neutralizing VEGF-A. After some disappointing results, research has centered on novel vectors, including optimized AAV2, AAV8 and lentivirus, as well as genes encoding other anti-angiogenic proteins, including ranibizumab, aflibercept, angiostatin and endostatin. Also, gene therapy targeting the complement system is being investigated for geographic atrophy due to non-neovascular AMD. Expert opinion: The success of gene therapy for AMD will depend on the selection of the most appropriate therapeutic protein and its level of chronic expression. Future investigations will center on optimizing vector, promoter and delivery methods, and evaluating the risks of the chronic expression of anti-angiogenic or anti-complement proteins.

Original languageEnglish (US)
Pages (from-to)1235-1244
Number of pages10
JournalExpert Opinion on Biological Therapy
Issue number10
StatePublished - Oct 3 2017


  • Adeno-associated virus
  • age-related macular degeneration
  • gene therapy
  • retina
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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