TY - JOUR
T1 - AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
AU - Ding, Kun
AU - Shen, Jikui
AU - Hafiz, Zibran
AU - Hackett, Sean F.
AU - e Silva, Raquel Lima
AU - Khan, Mahmood
AU - Lorenc, Valeria E.
AU - Chen, Daiqin
AU - Chadha, Rishi
AU - Zhang, Minie
AU - van Everen, Sherri
AU - Buss, Nicholas
AU - Fiscella, Michele
AU - Danos, Olivier
AU - Campochiaro, Peter A.
N1 - Funding Information:
Funding was provided by REGENXBIO Inc., the Alsheler-Durell Foundation, Per Bang-Jensen, Conrad and Lois Aschenbach, and Andrew and Yvette Marriott.
Publisher Copyright:
Copyright: © 2019, American Society for Clinical Investigation.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI129085
DO - 10.1172/JCI129085
M3 - Article
C2 - 31408444
AN - SCOPUS:85071280036
SN - 0021-9738
VL - 129
SP - 4901
EP - 4911
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -