Full metadata record
DC Field | Value | Language |
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dc.creator | Zabaleta-Lasarte, N. (Nerea) | - |
dc.creator | Barberia, M. (Miren) | - |
dc.creator | Martin-Higueras, C. (Cristina) | - |
dc.creator | Zapata-Linares, N.M. (Natalia María) | - |
dc.creator | Betancor, I. (Isabel) | - |
dc.creator | Rodriguez, S. (Saray) | - |
dc.creator | Martínez-Turrillas, R. (Rebeca) | - |
dc.creator | Torella, L. (Laura) | - |
dc.creator | Vales, A. (África) | - |
dc.creator | Olagüe, M. (María) | - |
dc.creator | Vilas, A. (Amaia) | - |
dc.creator | Castro-Labrador, L. (Laura) | - |
dc.creator | Lara-Astiaso, D. (David) | - |
dc.creator | Prosper-Cardoso, F. (Felipe) | - |
dc.creator | Salido, E. (Eduardo) | - |
dc.creator | González-Aseguinolaza, G. (Gloria) | - |
dc.creator | Rodriguez-Madoz, J.R. (Juan Roberto) | - |
dc.date.accessioned | 2019-02-01T08:45:26Z | - |
dc.date.available | 2019-02-01T08:45:26Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Zabaleta-Lasarte, N. (Nerea); Barberia, M.; Martin-Higueras, C.; et al. "CRISPR/Cas9-mediated glycolate oxidase disruption is an efficacious and safe treatment for primary hyperoxaluria type I". Nature communications. 9, 2018, 5454 | es |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://hdl.handle.net/10171/56384 | - |
dc.description.abstract | CRISPR/Cas9 technology offers novel approaches for the development of new therapies for many unmet clinical needs, including a significant number of inherited monogenic diseases. However, in vivo correction of disease-causing genes is still inefficient, especially for those diseases without selective advantage for corrected cells. We reasoned that substrate reduction therapies (SRT) targeting non-essential enzymes could provide an attractive alternative. Here we evaluate the therapeutic efficacy of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I (PH1), a rare inborn dysfunction in glyoxylate metabolism that results in excessive hepatic oxalate production causing end-stage renal disease. A single systemic administration of an AAV8-CRISPR/Cas9 vector targeting glycolate oxidase, prevents oxalate overproduction and kidney damage, with no signs of toxicity in Agxt1(-/-) mice. Our results reveal that CRISPR/Cas9-mediated SRT represents a promising therapeutic option for PH1 that can be potentially applied to other metabolic diseases caused by the accumulation of toxic metabolites. | - |
dc.description.sponsorship | We thank the Bioinformatics Unit at CIMA and the Genomics Facility at CIMA LABDiagnostics. This work was funded by grants from ERA-NET E-Rare 3 research programJTC ERAdicatPH, Instituto de Salud Carlos III (ISCIII) AC15/00036 and PI16/00150,TERCEL (ISCIII) RD16/0011/0005, MINECO SAF2015-69796, Gobierno de Navarra 91/2016, Ayuda a la investigación D. Juan Manuel Mingo and Oxalosis & HyperoxaluriaFoundation. NeZ was supported by fellowships form Asociación Amigos de la Uni-versidad de Navarra (ADA) and Fundación para la Investigación Médica Aplicada(FIMA). | - |
dc.language.iso | en | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | Substrate reduction therapy | - |
dc.subject | Mouse model | - |
dc.subject | Vivo | - |
dc.subject | Disease | - |
dc.subject | System | - |
dc.subject | Target | - |
dc.subject | Replacement | - |
dc.subject | Deficiency | - |
dc.subject | Expression | - |
dc.subject | Mutations | - |
dc.title | CRISPR/Cas9-mediated glycolate oxidase disruption is an efficacious and safe treatment for primary hyperoxaluria type I | - |
dc.type | info:eu-repo/semantics/article | - |
dc.description.note | This is an open access article distributed under the Creative Commons: Atribution License (cc BY) | - |
dc.identifier.doi | 10.1038/s41467-018-07827-1 | - |
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