Specific gene correction of the AGXT gene and direct cell reprogramming for the treatment of Primary Hyperoxaluria Type 1
Nieto-Romero, V. ; Garcia-Torralba, A. ; Molinos-Vicente, A. ; Garcia-Escudero, R. ; Pla-Palacin, I. ; Baptista, P.M. ; Salido, E. ; Segovia, J.C. ; Garcia-Bravo, M.
Resumen: P428
Primary Hyperoxaluria Type 1 (PH1) is an inherited rare metabolic liver disease caused by the deficiency in the alanine: glyoxylate aminotransferase enzyme (AGXT), involved in the glyoxylate metabolism. The only potentially curative treatment is organ transplantation. Thus, the development of new therapeutic approaches for the treatment of these patients appears as a priority.We propose the combination of site-specific gene correction and direct cell reprogramming for the generation of autologous phenotypically healthy induced hepatocytes (iHeps) from skin-derived fibroblast of PH1 patients. For the correction of AGXT mutations, we have designed specific gene editing tools to address gene correction by two different strategies, assisted by CRISPR/Cas9 system. Accurate specific point mutation correction (c.853T-C) has been achieved by homologydirected repair (HDR) with ssODN harbouring wild-type sequence. In the second strategy, an enhanced version ofAGXTcDNAhas been inserted near the transcription start codon of the endogenous gene, constituting an almost universal correction strategy for PH1 mutations. Direct reprogramming of fibroblasts has been conducted by overexpression of hepatic transcription factors and in vitro culture in defined media. In vitro characterization of healthy induced hepatocytes (iHeps) has demonstrated hepatic function of the reprogrammed cells. PH1 patient fibroblasts and , , ,
Idioma: Inglés
Año: 2019
Publicado en: HUMAN GENE THERAPY 30, 11 (2019), A144
ISSN: 1043-0342
Originalmente disponible en: Texto completo de la revista
Factor impacto JCR: 4.273 (2019)
Categ. JCR: BIOTECHNOLOGY & APPLIED MICROBIOLOGY rank: 30 / 156 = 0.192 (2019) - Q1 - T1
Categ. JCR: GENETICS & HEREDITY rank: 38 / 177 = 0.215 (2019) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 40 / 138 = 0.29 (2019) - Q2 - T1
Factor impacto SCIMAGO: 1.648 - Genetics (Q1) - Molecular Medicine (Q1) - Molecular Biology (Q2)
Tipo y forma: Comunicación congreso (Versión definitiva)
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Primary Hyperoxaluria Type 1 (PH1) is an inherited rare metabolic liver disease caused by the deficiency in the alanine: glyoxylate aminotransferase enzyme (AGXT), involved in the glyoxylate metabolism. The only potentially curative treatment is organ transplantation. Thus, the development of new therapeutic approaches for the treatment of these patients appears as a priority.We propose the combination of site-specific gene correction and direct cell reprogramming for the generation of autologous phenotypically healthy induced hepatocytes (iHeps) from skin-derived fibroblast of PH1 patients. For the correction of AGXT mutations, we have designed specific gene editing tools to address gene correction by two different strategies, assisted by CRISPR/Cas9 system. Accurate specific point mutation correction (c.853T-C) has been achieved by homologydirected repair (HDR) with ssODN harbouring wild-type sequence. In the second strategy, an enhanced version ofAGXTcDNAhas been inserted near the transcription start codon of the endogenous gene, constituting an almost universal correction strategy for PH1 mutations. Direct reprogramming of fibroblasts has been conducted by overexpression of hepatic transcription factors and in vitro culture in defined media. In vitro characterization of healthy induced hepatocytes (iHeps) has demonstrated hepatic function of the reprogrammed cells. PH1 patient fibroblasts and , , ,
Idioma: Inglés
Año: 2019
Publicado en: HUMAN GENE THERAPY 30, 11 (2019), A144
ISSN: 1043-0342
Originalmente disponible en: Texto completo de la revista
Factor impacto JCR: 4.273 (2019)
Categ. JCR: BIOTECHNOLOGY & APPLIED MICROBIOLOGY rank: 30 / 156 = 0.192 (2019) - Q1 - T1
Categ. JCR: GENETICS & HEREDITY rank: 38 / 177 = 0.215 (2019) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 40 / 138 = 0.29 (2019) - Q2 - T1
Factor impacto SCIMAGO: 1.648 - Genetics (Q1) - Molecular Medicine (Q1) - Molecular Biology (Q2)
Tipo y forma: Comunicación congreso (Versión definitiva)
Debe reconocer adecuadamente la autoría, proporcionar un enlace a la licencia e indicar si se han realizado cambios. Puede hacerlo de cualquier manera razonable, pero no de una manera que sugiera que tiene el apoyo del licenciador o lo recibe por el uso que hace. No puede utilizar el material para una finalidad comercial. Si remezcla, transforma o crea a partir del material, no puede difundir el material modificado.Exportado de SIDERAL (2021-01-26-15:08:58)
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Registro creado el 2021-01-26, última modificación el 2021-01-26