Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa

Background: Gene therapy is a therapeutic possibility for retinitis pigmentosa (RP), in which therapeutic transgenes are currently delivered to the retina by adeno-associated viral vectors (AAVs). Although their safety and efficacy have been demonstrated in both clinical and preclini-cal settings, A...

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Authors: Valdés-Sánchez, María Lourdes, Borrego-González, Sara, Montero-Sánchez, Adoración, Massalini, Simone, Cerda, Berta de la, Díaz Cuenca, Aránzazu, Díaz-Corrales, Francisco J.
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/283032
Online Access:http://hdl.handle.net/10261/283032
Access Level:Open access
Keyword:Retinitis pigmentosa
PRPF31
Gene therapy
Nanoparticles
Mesoporous silica
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spelling Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis PigmentosaValdés-Sánchez, María LourdesBorrego-González, SaraMontero-Sánchez, AdoraciónMassalini, SimoneCerda, Berta de laDíaz Cuenca, AránzazuDíaz-Corrales, Francisco J.Retinitis pigmentosaPRPF31Gene therapyNanoparticlesMesoporous silicaBackground: Gene therapy is a therapeutic possibility for retinitis pigmentosa (RP), in which therapeutic transgenes are currently delivered to the retina by adeno-associated viral vectors (AAVs). Although their safety and efficacy have been demonstrated in both clinical and preclini-cal settings, AAVs present some technical handicaps, such as limited cargo capacity and possible immunogenicity in repetitive doses. The development of alternative, non-viral delivery platforms like nanoparticles is of great interest to extend the application of gene therapy for RP. Methods: Amino-functionalized mesoporous silica-based nanoparticles (N-MSiNPs) were synthesized, physico-chemically characterized, and evaluated as gene delivery systems for human cells in vitro and for retinal cells in vivo. Transgene expression was evaluated by WB and immunofluorescence. The safety evaluation of mice subjected to subretinal injection was assessed by ophthalmological tests (electroretinogram, funduscopy, tomography, and optokinetic test). Results: N-MSiNPs delivered transgenes to human cells in vitro and to retinal cells in vivo. No adverse effects were detected for the integrity of the retinal tissue or the visual function of treated eyes. N-MSiNPs were able to deliver a therapeutic transgene candidate for RP, PRPF31, both in vitro and in vivo. Conclusions: N-MSiNPs are safe for retinal delivery and thus a potential alternative to viral vectors.This research was funded by the ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071, Consejería de Salud, Igualdad y Politicas Sociales (PI-0099-2018). ADC and SBG gratefully acknowledge the financial support provided by the Andalusian Ministry of Economy, Science, and Innovation (Proyecto Excelencia P10-CTS-6681).Molecular Diversity Preservation InternationalInstituto de Salud Carlos IIIEuropean CommissionJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/283032reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at 10.3390/jcm11082170http://dx.doi.org/10.3390/jcm11082170Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2830322026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
title Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
spellingShingle Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
Valdés-Sánchez, María Lourdes
Retinitis pigmentosa
PRPF31
Gene therapy
Nanoparticles
Mesoporous silica
title_short Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
title_full Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
title_fullStr Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
title_full_unstemmed Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
title_sort Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa
dc.creator.none.fl_str_mv Valdés-Sánchez, María Lourdes
Borrego-González, Sara
Montero-Sánchez, Adoración
Massalini, Simone
Cerda, Berta de la
Díaz Cuenca, Aránzazu
Díaz-Corrales, Francisco J.
author Valdés-Sánchez, María Lourdes
author_facet Valdés-Sánchez, María Lourdes
Borrego-González, Sara
Montero-Sánchez, Adoración
Massalini, Simone
Cerda, Berta de la
Díaz Cuenca, Aránzazu
Díaz-Corrales, Francisco J.
author_role author
author2 Borrego-González, Sara
Montero-Sánchez, Adoración
Massalini, Simone
Cerda, Berta de la
Díaz Cuenca, Aránzazu
Díaz-Corrales, Francisco J.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Retinitis pigmentosa
PRPF31
Gene therapy
Nanoparticles
Mesoporous silica
topic Retinitis pigmentosa
PRPF31
Gene therapy
Nanoparticles
Mesoporous silica
description Background: Gene therapy is a therapeutic possibility for retinitis pigmentosa (RP), in which therapeutic transgenes are currently delivered to the retina by adeno-associated viral vectors (AAVs). Although their safety and efficacy have been demonstrated in both clinical and preclini-cal settings, AAVs present some technical handicaps, such as limited cargo capacity and possible immunogenicity in repetitive doses. The development of alternative, non-viral delivery platforms like nanoparticles is of great interest to extend the application of gene therapy for RP. Methods: Amino-functionalized mesoporous silica-based nanoparticles (N-MSiNPs) were synthesized, physico-chemically characterized, and evaluated as gene delivery systems for human cells in vitro and for retinal cells in vivo. Transgene expression was evaluated by WB and immunofluorescence. The safety evaluation of mice subjected to subretinal injection was assessed by ophthalmological tests (electroretinogram, funduscopy, tomography, and optokinetic test). Results: N-MSiNPs delivered transgenes to human cells in vitro and to retinal cells in vivo. No adverse effects were detected for the integrity of the retinal tissue or the visual function of treated eyes. N-MSiNPs were able to deliver a therapeutic transgene candidate for RP, PRPF31, both in vitro and in vivo. Conclusions: N-MSiNPs are safe for retinal delivery and thus a potential alternative to viral vectors.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/283032
url http://hdl.handle.net/10261/283032
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.3390/jcm11082170
http://dx.doi.org/10.3390/jcm11082170
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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