Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.
Lavin, Peter J
Winn, Michelle P
Kemper, Alex R
Brown, Talmage T
Koeberl, Dwight D
AffiliationDepartment of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Disease Models, Animal
Gene Expression Regulation
Glycogen Storage Disease Type I
MetadataShow full item record
CitationHepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. 2011, 19 (11):1961-70 Mol. Ther.
JournalMolecular therapy : the journal of the American Society of Gene Therapy
AbstractGlycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7, dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.
- Long-term efficacy following readministration of an adeno-associated virus vector in dogs with glycogen storage disease type Ia.
- Authors: Demaster A, Luo X, Curtis S, Williams KD, Landau DJ, Drake EJ, Kozink DM, Bird A, Crane B, Sun F, Pinto CR, Brown TT, Kemper AR, Koeberl DD
- Issue date: 2012 Apr
- AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia.
- Authors: Koeberl DD, Pinto C, Sun B, Li S, Kozink DM, Benjamin DK Jr, Demaster AK, Kruse MA, Vaughn V, Hillman S, Bird A, Jackson M, Brown T, Kishnani PS, Chen YT
- Issue date: 2008 Apr
- Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia.
- Authors: Koeberl DD, Sun BD, Damodaran TV, Brown T, Millington DS, Benjamin DK Jr, Bird A, Schneider A, Hillman S, Jackson M, Beaty RM, Chen YT
- Issue date: 2006 Sep
- Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer.
- Authors: Ghosh A, Allamarvdasht M, Pan CJ, Sun MS, Mansfield BC, Byrne BJ, Chou JY
- Issue date: 2006 Feb
- The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.
- Authors: Lee YM, Pan CJ, Koeberl DD, Mansfield BC, Chou JY
- Issue date: 2013 Nov