July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Suprachoroidal AAV8-Vectored Gene Transfer Provides Widespread Transgene Expression in RPE and Retina
Author Affiliations & Notes
  • Kun Ding
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Jikui Shen
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Zibran Hafiz
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Sean Hackett
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Raquel Formica
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Valeria E Lorenc
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Rishi Chadha
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Minie Zhang
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Sherri Van Everen
    Regenxbio, Maryland, United States
  • Nicholas Buss
    Regenxbio, Maryland, United States
  • Michele Fiscella
    Regenxbio, Maryland, United States
  • Olivier Danos
    Regenxbio, Maryland, United States
  • Peter A Campochiaro
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Kun Ding, RegenxBio (F); Jikui Shen, RegenxBio (F); Zibran Hafiz, RegenxBio (F); Sean Hackett, RegenxBio (F); Raquel Formica, RegenxBio (F); Valeria Lorenc, RegenxBio (F); Rishi Chadha, RegenxBio (F); Minie Zhang, RegenxBio (F); Sherri Everen, RegenxBio (E); Nicholas Buss, RegenxBio (E); Michele Fiscella, RegenxBio (E); Olivier Danos, RegenxBio (E); Peter Campochiaro, RegenxBio (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2923. doi:https://doi.org/
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    • Get Citation

      Kun Ding, Jikui Shen, Zibran Hafiz, Sean Hackett, Raquel Formica, Valeria E Lorenc, Rishi Chadha, Minie Zhang, Sherri Van Everen, Nicholas Buss, Michele Fiscella, Olivier Danos, Peter A Campochiaro; Suprachoroidal AAV8-Vectored Gene Transfer Provides Widespread Transgene Expression in RPE and Retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2923. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the potential value of suprachoroidal injection of AAV8 vectors for ocular gene transfer

Methods : Suprachoroidal or subretinal injection of 2.85 x1010 gene copies (GC) of AAV8.GFP or RGX-314 (AAV8.antiVEGFfab) was done in Norway Brown rats (n=40) and suprachoroidal injection of 4.75 x1011 GC of AAV8.GFP was done in Rhesus macaques (n=3). Retina and RPE/choroid flat mounts or ocular sections were examined by fluorescence microscopy. GFP protein, antiVEGFfab and albumin levels to evaluate vascular leakage were measured by ELISA. At 2 or 7 weeks after suprachroidal or subretinal injection of RGX-314, an intravitreous injection of VEGF165 given to induce leakage and after 24 hours vitreous albumin was measured.

Results : Two weeks after a single suprachoroidal injection of AAV8.GFP in rats, there was strong GFP fluorescence covering 23% of RPE/choroid flat mounts. Ocular sections showed GFP fluorescence around the entire circumference of the equator of the eye throughout the choroid, RPE, and all layers of the retina. Two suprachoroidal injections of AAV8.GFP in the same eye resulted in GFP fluorescence covering 42% of the area of RPE/choroid flat mounts. VEGF-induced increase in vitreous albumin was significantly and similarly reduced 2 or 7 weeks after suprachoroidal or subretinal injection of RGX-314. AntiVEGFfab transgene protein levels were equally high for the surpachoroidal and subretinal route. Three weeks after a single suprachoroidal injection of AAV8.GFP in NHPs, there was strong expression of GFP throughout approximately 1/3 of the retina and RPE/choroid.

Conclusions : Widespread transduction of all layers of the retina and suppression of VEGF-induced vascular leakage indicate that suprachoroidal delivery has the potential to provide similar results to subretinal delivery and should be further explored for AAV8-vectored ocular gene transfer.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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