Delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type Ia, with adeno-associated virus (AAV) vectors
| Autor: | Yuan-Tsong Chen, Priya S. Kishnani, Denise Peterson, Talmage T. Brown, Daniel K. Benjamin, T Juopperi, Mark W. Jackson, R. M. Beaty, Anne Boney, Dwight D. Koeberl, Andrew Bird |
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| Rok vydání: | 2002 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Time Factors Genetic enhancement Genetic Vectors Glycogen Storage Disease Type I Biology medicine.disease_cause Virus chemistry.chemical_compound Dogs Transduction Genetic Internal medicine Genetics medicine Animals Glycogen storage disease Lactic Acid Vector (molecular biology) Molecular Biology Adeno-associated virus Triglycerides Glycogen Genetic transfer Genetic Therapy Dependovirus medicine.disease Adenoviridae Cholesterol Endocrinology Liver chemistry Models Animal Glucose-6-Phosphatase Molecular Medicine |
| Zdroj: | Gene Therapy. 9:1015-1022 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | Therapy in glycogen storage disease type Ia (GSD Ia), an inherited disorder of carbohydrate metabolism, relies on nutritional support that postpones but fails to prevent long-term complications of GSD Ia. In the canine model for GSD Ia, we evaluated the potential of intravenously delivered adeno-associated virus (AAV) vectors for gene therapy. In three affected canines, liver glycogen was reduced following hepatic expression of canine glucose-6-phosphatase (G6Pase). Two months after AAV vector administration, one affected dog had normalization of fasting glucose, cholesterol, triglycerides, and lactic acid. Concatamerized AAV vector DNA was confirmed by Southern blot analysis of liver DNA isolated from treated dogs, as head-to-tail, head-to-head, and tail-to-tail concatamers. Six weeks after vector administration, the level of vector DNA signal in each dog varied from one to five copies per cell, consistent with variation in the efficiency of transduction within the liver. AAV vector administration in the canine model for GSD Ia resulted in sustained G6Pase expression and improvement in liver histology and in biochemical parameters. |
| Databáze: | OpenAIRE |
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