Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates

C. M. Lai, M. J. Estcourt, R. P. Himbeck, S. Y. Lee, I. Yew-San Yeo, C. Luu, B. K. Loh, M. W. Lee, A. Barathi, J. Villano, C. L. Ang, R. G. Van Der Most, I. J. Constable, D. Dismuke, R. J. Samulski, M. A. Degli-Esposti, E. P. Rakoczy

Research output: Contribution to journalArticlepeer-review


We report on the long-term safety of AAV2.sFlt-1 (a recombinant adeno-associated virus serotype 2 carrying the soluble form of the Flt-1 receptor) injection into the subretinal space of non-human primates. Levels of sFlt-1 protein were significantly higher (P0.05) in the vitreous of four out of five AAV2.sFlt-1-injected eyes. There was no evidence of damage to the eyes of animals that received subretinal injections of AAV2.sFlt-1; ocular examination showed no anterior chamber flare, normal fundus and electroretinography responses equivalent to those observed before treatment. Notably, immunological analysis demonstrated that gene therapy involving subretinal injection of AAV2.sFlt-1 does not elicit cell-mediated immunity. Biodistribution analysis showed that AAV2.sFlt-1 could be detected only in the eye and not in the other organs tested. These data indicate that gene therapy with subretinal AAV2.sFlt-1 is safe and well tolerated, and therefore promising for the long-term treatment of neovascular diseases of the eye.

Original languageEnglish (US)
Pages (from-to)999-1009
Number of pages11
JournalGene Therapy
Issue number10
StatePublished - Oct 2012
Externally publishedYes


  • Immunology
  • Neovascularization
  • Retinal diseases

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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