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Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria
- Source :
- Experimentalmolecular medicine. 38(6)
- Publication Year :
- 2007
-
Abstract
- Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine beta-synthase (CBS). The major clinical symptoms of this disease are mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms, and skeletal deformities. The major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. There is currently no effective long-term treatment to lower the elevated plasma levels of homocysteine. However, gene therapy could be an effective novel approach for the treatment of homocystinuria. A recombinant adeno- associated virus vector carrying human CBS cDNA (rAAV-hCBS) was constructed and administered to CBS-/- mice by intramuscular (IM) and intraperitoneal (IP) injections. Serum homocysteine concentrations significantly decreased in treated mice compared with age-matched controls two weeks after treatment. The treated CBS-/- mice had life spans 3-7 days longer compared with untreated CBS-/- mice. In CBS-/- mice treated with rAAV-hCBS via IP injection, the vector was detected in all organs examined including liver, spleen, and kidney, and CBS gene expression was observed by immunohistochemical staining in the liver. These results indicate the efficacy of gene delivery and demonstrate the possibility of gene therapy mediated by AAV gene transfer in this mouse model of homocystinuria.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Homocysteine
Genetic enhancement
Clinical Biochemistry
DNA, Recombinant
Cystathionine beta-Synthase
Homocystinuria
Gene delivery
Biology
medicine.disease_cause
Biochemistry
Viral vector
Cell Line
chemistry.chemical_compound
Mice
Internal medicine
medicine
Animals
Humans
Molecular Biology
Adeno-associated virus
Metabolic disorder
Gene Transfer Techniques
Genetic Therapy
Dependovirus
medicine.disease
Cystathionine beta synthase
Immunohistochemistry
Survival Rate
Disease Models, Animal
Endocrinology
chemistry
biology.protein
Molecular Medicine
Subjects
Details
- ISSN :
- 12263613
- Volume :
- 38
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Experimentalmolecular medicine
- Accession number :
- edsair.doi.dedup.....0af07467b479b88813431c889504cf43