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Title: | Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications | Authors: | Rebelo, Catarina Reis, Tiago Guedes, Joana Saraiva, Cláudia Rodrigues, Artur Filipe Simões, Susana Bernardino, Liliana Peça, João Pinho, Sónia L. C. Ferreira, Lino |
Issue Date: | 2022 | Publisher: | Nature | Project: | POCI-01-0145-FEDER-016390:CANCEL STEM info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/NAN-MAT/28060/2017/PT/BrainEdition: remotely controlling gene edition in neural stem cells POCI-01-0145- FEDER-016682 info:eu-repo/grantAgreement/CENTRO-01-0145-FEDER-000014/PT Interreg 2IQBioNeuro info:eu-repo/grantAgreement/EC/H2020/669088/EU/Enhancing Research in Ageing at the University of Coimbra EAPA_791/2018 - NEUROATLANTIC entitled: ‘An Atlantic innovation platform on diagnosis and treatment of neurological diseases and aging’ info:eu-repo/grantAgreement/EC/H2020/952266/EU/RESEarch for healThy AGEING info:eu-repo/grantAgreement/FCT/OE/PD/BD/52337/2013/PT/Nanomedicine to enhance heart regenerative potential info:eu-repo/grantAgreement/FCT/FARH/SFRH/BPD/96048/2013/PT/Cellular reprogramming by near infrared NIR-activatable nanoparticles containing transcription factors - NanoTarget: remote modulation for cardiac progenitor cells info:eu-repo/grantAgreement/EC/H2020/101003413/EU/LIght-responsive GrapHene-based inTerfaces for Electrical STimulation |
Serial title, monograph or event: | Nature Communications | Volume: | 13 | Issue: | 1 | Abstract: | 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). | URI: | https://hdl.handle.net/10316/101264 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-022-31791-6 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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s41467-022-31791-6.pdf | 2.23 MB | Adobe PDF | View/Open |
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