Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) which catalyzes conversion of glyoxylate into glycine. AGT deficiency results in overproduction of oxalate which ultimately leads to end-stage renal disease and death. Organ transplantation as either preemptive liver transplantation or combined liver/kidney transplantation is the only available therapy to prevent disease progression. Gene therapy is an attractive option to provide an alternative treatment for PH1. Towards this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. Compared to saline controls, AGT-deficient mice injected with an HDAd encoding the AGT under the control of a liver-specific promoter showed a significant reduction of hyperoxaluria and less increase of urinary oxalate following challenge with Ethylene Glycol (EG), a precursor of glyoxylate. These studies may thus pave the way to clinical application of HDAd for PH1 gene therapy.Gene Therapy accepted article preview online, 26 November 2015. doi:10.1038/gt.2015.107.

Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1 / Castello, R; Borzone, Roberta; D'Aria, S; Annunziata, P; Piccolo, P; BRUNETTI PIERRI, Nicola. - In: GENE THERAPY. - ISSN 0969-7128. - (2015). [10.1038/gt.2015.107]

Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1

Piccolo, P;BRUNETTI PIERRI, NICOLA
2015

Abstract

Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) which catalyzes conversion of glyoxylate into glycine. AGT deficiency results in overproduction of oxalate which ultimately leads to end-stage renal disease and death. Organ transplantation as either preemptive liver transplantation or combined liver/kidney transplantation is the only available therapy to prevent disease progression. Gene therapy is an attractive option to provide an alternative treatment for PH1. Towards this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. Compared to saline controls, AGT-deficient mice injected with an HDAd encoding the AGT under the control of a liver-specific promoter showed a significant reduction of hyperoxaluria and less increase of urinary oxalate following challenge with Ethylene Glycol (EG), a precursor of glyoxylate. These studies may thus pave the way to clinical application of HDAd for PH1 gene therapy.Gene Therapy accepted article preview online, 26 November 2015. doi:10.1038/gt.2015.107.
2015
Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1 / Castello, R; Borzone, Roberta; D'Aria, S; Annunziata, P; Piccolo, P; BRUNETTI PIERRI, Nicola. - In: GENE THERAPY. - ISSN 0969-7128. - (2015). [10.1038/gt.2015.107]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/613845
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