Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/46097
Título: Phenotypic correction of a mouse model for primary hyperoxaluria with adeno-associated virus gene transfer
Autores/as: Salido, Eduardo
Rodriguez-Pena, Marisol
Santana, Alfredo 
Beattie, Stuart G.
Petry, Harald
Torres, Armando
Clasificación UNESCO: 32 Ciencias médicas
320102 Genética clínica
Palabras clave: Mouse Model
Hyperoxaluria
Virus Gene Transfer
Fecha de publicación: 2011
Publicación seriada: Molecular Therapy 
Resumen: Primary hyperoxaluria type I (PH1) is an inborn error of metabolism caused by deficiency of the hepatic enzyme alanine-glyoxylate aminotransferase (AGXT or AGT) which leads to overproduction of oxalate by the liver and subsequent urolithiasis and renal failure. The current therapy largely depends on liver transplantation, which is associated with significant morbidity and mortality. To explore an alternative treatment, we used somatic gene transfer in a mouse genetic model for PH1 (Agxt1KO). Recombinant adeno-associated virus (AAV) vectors containing the human AGXT complementary DNA (cDNA) were pseudotyped with capsids from either serotype 8 or 5, and delivered to the livers of Agxt1KO mice via the tail vein. Both AAV8-AGXT and AAV5-AGXT vectors were able to reduce oxaluria to normal levels. In addition, treated mice showed blunted increase of oxaluria after challenge with ethylene glycol (EG), a glyoxylate precursor. In mice, AGT enzyme activity in whole liver extracts were restored to normal without hepatic toxicity nor immunogenicity for the 50 day follow-up. In summary, this study demonstrates the correction of primary hyperoxaluria in mice treated with either AAV5 or AAV8 vectors.
URI: http://hdl.handle.net/10553/46097
ISSN: 1525-0016
DOI: 10.1038/mt.2010.270
Fuente: Molecular Therapy [ISSN 1525-0016],v. 19, p. 870-875
Colección:Artículos
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