AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Kun Ding, Jikui Shen, Zibran Hafiz, Sean F. Hackett, Raquel Lima E Silva, Mahmood Khan, Valeria E. Lorenc, Daiqin Chen, Rishi Chadha, Minie Zhang, Sherri Van Everen, Nicholas Buss, Michele Fiscella, Olivier Danos, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8.GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti-VEGF Fab and similar suppression of VEGF-induced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE.

Original languageEnglish (US)
JournalThe Journal of clinical investigation
Volume130
DOIs
StatePublished - Aug 13 2019

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Transgenes
Injections
Epithelium
Genes
Vascular Endothelial Growth Factor A
Genetic Therapy
Retina
Outpatients
Fluorescence
Primates
Blood Vessels
Swine

Keywords

  • Gene therapy
  • Ophthalmology

ASJC Scopus subject areas

  • Medicine(all)

Cite this

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. / Ding, Kun; Shen, Jikui; Hafiz, Zibran; Hackett, Sean F.; Lima E Silva, Raquel; Khan, Mahmood; Lorenc, Valeria E.; Chen, Daiqin; Chadha, Rishi; Zhang, Minie; Van Everen, Sherri; Buss, Nicholas; Fiscella, Michele; Danos, Olivier; Campochiaro, Peter A.

In: The Journal of clinical investigation, Vol. 130, 13.08.2019.

Research output: Contribution to journalArticle

Ding, K, Shen, J, Hafiz, Z, Hackett, SF, Lima E Silva, R, Khan, M, Lorenc, VE, Chen, D, Chadha, R, Zhang, M, Van Everen, S, Buss, N, Fiscella, M, Danos, O & Campochiaro, PA 2019, 'AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression', The Journal of clinical investigation, vol. 130. https://doi.org/10.1172/JCI129085
Ding, Kun ; Shen, Jikui ; Hafiz, Zibran ; Hackett, Sean F. ; Lima E Silva, Raquel ; Khan, Mahmood ; Lorenc, Valeria E. ; Chen, Daiqin ; Chadha, Rishi ; Zhang, Minie ; Van Everen, Sherri ; Buss, Nicholas ; Fiscella, Michele ; Danos, Olivier ; Campochiaro, Peter A. / AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. In: The Journal of clinical investigation. 2019 ; Vol. 130.
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