AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Autores
Ding, Kun; Shen, Jikui; Hafiz, Zibran; Hackett, Sean F.; Lima e Silva, Raquel; Khan, Mahmood; Lorenc, Valeria Erika; Chen, Daiqin; Chadha, Rishi; Zhang, Minie; van Everen, Sherri; Buss, Nicholas; Fiscella, Michele; Danos, Olivier; Campochiaro, Peter A.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Ding, Kun. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Shen, Jikui. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Hafiz, Zibran. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Hackett, Sean F.. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Lima e Silva, Raquel. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Khan, Mahmood. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Lorenc, Valeria Erika. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Chen, Daiqin. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Chadha, Rishi. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Zhang, Minie. Johns Hopkins University School of Medicine; Estados Unidos
Fil: van Everen, Sherri. No especifíca;
Fil: Buss, Nicholas. No especifíca;
Fil: Fiscella, Michele. No especifíca;
Fil: Danos, Olivier. No especifíca;
Fil: Campochiaro, Peter A.. Johns Hopkins University School of Medicine; Estados Unidos
Materia
AAV8
suprachoroidal
gene transfer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/163896
Acceder
id CONICETDig_b83e9488d38e03ed8d3f41530e69dad0
oai_identifier_str oai:ri.conicet.gov.ar:11336/163896
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expressionDing, KunShen, JikuiHafiz, ZibranHackett, Sean F.Lima e Silva, RaquelKhan, MahmoodLorenc, Valeria ErikaChen, DaiqinChadha, RishiZhang, Minievan Everen, SherriBuss, NicholasFiscella, MicheleDanos, OlivierCampochiaro, Peter A.AAV8suprachoroidalgene transferhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1There 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.Fil: Ding, Kun. Johns Hopkins University School of Medicine; Estados UnidosFil: Shen, Jikui. Johns Hopkins University School of Medicine; Estados UnidosFil: Hafiz, Zibran. Johns Hopkins University School of Medicine; Estados UnidosFil: Hackett, Sean F.. Johns Hopkins University School of Medicine; Estados UnidosFil: Lima e Silva, Raquel. Johns Hopkins University School of Medicine; Estados UnidosFil: Khan, Mahmood. Johns Hopkins University School of Medicine; Estados UnidosFil: Lorenc, Valeria Erika. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Chen, Daiqin. Johns Hopkins University School of Medicine; Estados UnidosFil: Chadha, Rishi. Johns Hopkins University School of Medicine; Estados UnidosFil: Zhang, Minie. Johns Hopkins University School of Medicine; Estados UnidosFil: van Everen, Sherri. No especifíca;Fil: Buss, Nicholas. No especifíca;Fil: Fiscella, Michele. No especifíca;Fil: Danos, Olivier. No especifíca;Fil: Campochiaro, Peter A.. Johns Hopkins University School of Medicine; Estados UnidosAmerican Society for Clinical Investigation2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/163896Ding, Kun; Shen, Jikui; Hafiz, Zibran; Hackett, Sean F.; Lima e Silva, Raquel; et al.; AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression; American Society for Clinical Investigation; Journal of Clinical Investigation; 129; 11; 11-2019; 4901-49110021-9738CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1172/JCI129085info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:25:28Zoai:ri.conicet.gov.ar:11336/163896instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:25:28.956CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
title AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
spellingShingle AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
Ding, Kun
AAV8
suprachoroidal
gene transfer
title_short AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
title_full AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
title_fullStr AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
title_full_unstemmed AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
title_sort AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
dc.creator.none.fl_str_mv Ding, Kun
Shen, Jikui
Hafiz, Zibran
Hackett, Sean F.
Lima e Silva, Raquel
Khan, Mahmood
Lorenc, Valeria Erika
Chen, Daiqin
Chadha, Rishi
Zhang, Minie
van Everen, Sherri
Buss, Nicholas
Fiscella, Michele
Danos, Olivier
Campochiaro, Peter A.
author Ding, Kun
author_facet Ding, Kun
Shen, Jikui
Hafiz, Zibran
Hackett, Sean F.
Lima e Silva, Raquel
Khan, Mahmood
Lorenc, Valeria Erika
Chen, Daiqin
Chadha, Rishi
Zhang, Minie
van Everen, Sherri
Buss, Nicholas
Fiscella, Michele
Danos, Olivier
Campochiaro, Peter A.
author_role author
author2 Shen, Jikui
Hafiz, Zibran
Hackett, Sean F.
Lima e Silva, Raquel
Khan, Mahmood
Lorenc, Valeria Erika
Chen, Daiqin
Chadha, Rishi
Zhang, Minie
van Everen, Sherri
Buss, Nicholas
Fiscella, Michele
Danos, Olivier
Campochiaro, Peter A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AAV8
suprachoroidal
gene transfer
topic AAV8
suprachoroidal
gene transfer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Ding, Kun. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Shen, Jikui. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Hafiz, Zibran. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Hackett, Sean F.. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Lima e Silva, Raquel. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Khan, Mahmood. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Lorenc, Valeria Erika. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Chen, Daiqin. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Chadha, Rishi. Johns Hopkins University School of Medicine; Estados Unidos
Fil: Zhang, Minie. Johns Hopkins University School of Medicine; Estados Unidos
Fil: van Everen, Sherri. No especifíca;
Fil: Buss, Nicholas. No especifíca;
Fil: Fiscella, Michele. No especifíca;
Fil: Danos, Olivier. No especifíca;
Fil: Campochiaro, Peter A.. Johns Hopkins University School of Medicine; Estados Unidos
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/163896
Ding, Kun; Shen, Jikui; Hafiz, Zibran; Hackett, Sean F.; Lima e Silva, Raquel; et al.; AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression; American Society for Clinical Investigation; Journal of Clinical Investigation; 129; 11; 11-2019; 4901-4911
0021-9738
CONICET Digital
CONICET
url http://hdl.handle.net/11336/163896
identifier_str_mv Ding, Kun; Shen, Jikui; Hafiz, Zibran; Hackett, Sean F.; Lima e Silva, Raquel; et al.; AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression; American Society for Clinical Investigation; Journal of Clinical Investigation; 129; 11; 11-2019; 4901-4911
0021-9738
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI129085
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842981411690119168
score 12.993085

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