Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/101264 https://doi.org/10.1038/s41467-022-31791-6 |
Resumo: | Spatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape. This formulation allows in vitro spatial control in gene editing after activation with near-infrared light. We further demonstrate the potential of this formulation in vivo through three different paradigms: (i) gene editing in neurogenic niches, (ii) gene editing in the ventral tegmental area to facilitate monitoring of edited cells by precise optogenetic control of reward and reinforcement, and (iii) gene editing in a localized brain region via a noninvasive administration route (i.e., intranasal). |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applicationsBrainInfrared RaysOptogeneticsProteinsGene EditingNanoparticlesSpatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape. This formulation allows in vitro spatial control in gene editing after activation with near-infrared light. We further demonstrate the potential of this formulation in vivo through three different paradigms: (i) gene editing in neurogenic niches, (ii) gene editing in the ventral tegmental area to facilitate monitoring of edited cells by precise optogenetic control of reward and reinforcement, and (iii) gene editing in a localized brain region via a noninvasive administration route (i.e., intranasal).Nature2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/101264http://hdl.handle.net/10316/101264https://doi.org/10.1038/s41467-022-31791-6eng2041-1723Rebelo, CatarinaReis, TiagoGuedes, JoanaSaraiva, CláudiaRodrigues, Artur FilipeSimões, SusanaBernardino, LilianaPeça, JoãoPinho, Sónia L. C.Ferreira, Linoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-02-21T11:40:47Zoai:estudogeral.uc.pt:10316/101264Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:18:29.788134Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
title |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
spellingShingle |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications Rebelo, Catarina Brain Infrared Rays Optogenetics Proteins Gene Editing Nanoparticles |
title_short |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
title_full |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
title_fullStr |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
title_full_unstemmed |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
title_sort |
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications |
author |
Rebelo, Catarina |
author_facet |
Rebelo, Catarina Reis, Tiago Guedes, Joana Saraiva, Cláudia Rodrigues, Artur Filipe Simões, Susana Bernardino, Liliana Peça, João Pinho, Sónia L. C. Ferreira, Lino |
author_role |
author |
author2 |
Reis, Tiago Guedes, Joana Saraiva, Cláudia Rodrigues, Artur Filipe Simões, Susana Bernardino, Liliana Peça, João Pinho, Sónia L. C. Ferreira, Lino |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Rebelo, Catarina Reis, Tiago Guedes, Joana Saraiva, Cláudia Rodrigues, Artur Filipe Simões, Susana Bernardino, Liliana Peça, João Pinho, Sónia L. C. Ferreira, Lino |
dc.subject.por.fl_str_mv |
Brain Infrared Rays Optogenetics Proteins Gene Editing Nanoparticles |
topic |
Brain Infrared Rays Optogenetics Proteins Gene Editing Nanoparticles |
description |
Spatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape. This formulation allows in vitro spatial control in gene editing after activation with near-infrared light. We further demonstrate the potential of this formulation in vivo through three different paradigms: (i) gene editing in neurogenic niches, (ii) gene editing in the ventral tegmental area to facilitate monitoring of edited cells by precise optogenetic control of reward and reinforcement, and (iii) gene editing in a localized brain region via a noninvasive administration route (i.e., intranasal). |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/101264 http://hdl.handle.net/10316/101264 https://doi.org/10.1038/s41467-022-31791-6 |
url |
http://hdl.handle.net/10316/101264 https://doi.org/10.1038/s41467-022-31791-6 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Nature |
publisher.none.fl_str_mv |
Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134079692570624 |