(Institución)
 
 

Docu-menta > Investigación Básica > Artículos de Investigación Básica >

Por favor, use este identificador para citar o enlazar este ítem: http://documenta.ciemat.es/handle/123456789/2919

Título : Restored glyoxylate metabolism after AGXT gene correction and direct reprogramming of primary hyperoxaluria type 1 fibroblasts
Autor : Nieto-Romero, Virginia
García-Torralba, Aida
Molinos-Vicente, Andrea
Moya, Francisco José
García-Escudero, Ramón
Salido, Eduardo
Segovia, José Carlos
García-Bravo, María
Palabras clave : Hyperoxaluria
AGXT
Gene editing
CRISPR/Cas9
Homology directed repair
Hepatic reprogramming
Induced-hepatocytes
Oxalate
In vitro disease model
Fecha de publicación : 24-abr-2024
Resumen : Primary Hyperoxaluria Type 1 (PH1) is a rare inherited metabolic disorder characterized by oxalate overproduction in the liver, resulting in renal damage. It is caused by mutations in the AGXT gene. Combined liver and kidney transplantation is currently the only permanent curative treatment. We combined locus-specific gene correction and hepatic direct cell reprogramming to generate autologous healthy induced hepatocytes (iHeps) from PH1 patient-derived fibroblasts. First, site-specific AGXT corrected cells were obtained by homology directed repair (HDR) assisted by CRISPR/Cas9, following two different strategies: accurate point mutation (c.731T>C) correction or knock-in of an enhanced version of AGXT cDNA. Then, iHeps were generated, by overexpression of hepatic transcription factors. Generated AGXT-corrected iHeps showed hepatic gene expression profile and exhibited in vitro reversion of oxalate accumulation compared to non-edited PH1-derived iHeps. This strategy set up a potential alternative cellular source for liver cell replacement therapy and a personalized PH1 in vitro disease model.
URI : http://documenta.ciemat.es/handle/123456789/2919
ISSN : 25890042
Aparece en las colecciones: Artículos de Investigación Básica

Ficheros en este ítem:

Fichero Descripción Tamaño Formato
28. Nieto-Romero- iSCIENCE 2024.pdf6.09 MBAdobe PDFVisualizar/Abrir
View Statistics

Los ítems de Docu-menta están protegidos por una Licencia Creative Commons, con derechos reservados.

 

Información y consultas: documenta@ciemat.es | Documento legal