Ab-externo AAV-mediated gene delivery to the suprachoroidal space using a 250 micron flexible microcatheter

Marc C. Peden, Jeff Min, Craig Meyers, Zachary Lukowski, Qiuhong Li, Sanford L. Boye, Monica Levine, William W. Hauswirth, Ramakrishna Ratnakaram, William Dawson, Wesley C. Smith, Mark B. Sherwood

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background: The current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ab externo approach that utilizes an illuminated microcatheter. Methods: 6 New Zealand White rabbits and 2 Dutch Belted rabbits were used to evaluate the ab externo delivery method. sc-AAV5-smCBA-hGFP vector was delivered into the suprachoroidal space using an illuminated iTrackTM 250A microcatheter. Six weeks after surgery, the rabbits were sacrificed and their eyes evaluated for AAV transfection using immunofluorescent antibody staining of GFP. Results: Immunostaining of sectioned and whole-mounted eyes demonstrated robust transfection in all treated eyes, with no fluorescence in untreated control eyes. Transfection occurred diffusely and involved both the choroid and the retina. No apparent adverse effects caused by either the viral vector or the procedure itself could be seen either clinically or histologically. Conclusions: The ab externo method of delivery using a microcatheter was successful in safely and effectively delivering a gene therapy agent to the suprachoroidal space. This method presents a less invasive alternative to the current method of virally vectored gene delivery.

Original languageEnglish (US)
Article numbere17140
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Peden, M. C., Min, J., Meyers, C., Lukowski, Z., Li, Q., Boye, S. L., Levine, M., Hauswirth, W. W., Ratnakaram, R., Dawson, W., Smith, W. C., & Sherwood, M. B. (2011). Ab-externo AAV-mediated gene delivery to the suprachoroidal space using a 250 micron flexible microcatheter. PloS one, 6(2), [e17140]. https://doi.org/10.1371/journal.pone.0017140