ArticleThe journal of gene medicine2008
Improved retroviral vector design results in sustained expression after adult gene therapy in mucopolysaccharidosis I mice.
Article in The journal of gene medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Mucopolysaccharidoses type I gene therapy.Journal of inherited metabolic disease · 2021Review
- Comparative Effectiveness of Intracerebroventricular, Intrathecal, and Intranasal Routes of AAV9 Vector Administration for Genetic Therapy of Neurologic Disease in Murine Mucopolysaccharidosis Type I.Frontiers in molecular neuroscience · 2021Article
- Failures of Endochondral Ossification in the Mucopolysaccharidoses.Current osteoporosis reports · 2020Review
- Review
- Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases.Genetics and molecular biology · 2019Article
- Liver-Directed Human Amniotic Epithelial Cell Transplantation Improves Systemic Disease Phenotype in Hurler Syndrome Mouse Model.Stem cells translational medicine · 2017Article
- Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology.Journal of inherited metabolic disease · 2017Article
- Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier.Molecular genetics and metabolism · 2015Review
- Therapies for the bone in mucopolysaccharidoses.Molecular genetics and metabolism · 2015Review
- Standardization of α-L-iduronidase enzyme assay with Michaelis-Menten kinetics.Molecular genetics and metabolism · 2014Article
- Therapies of mucopolysaccharidosis IVA (Morquio A syndrome).Expert opinion on orphan drugs · 2013Article
- Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII.Journal of inherited metabolic disease · 2013Article
- Treatment of adult MPSI mouse brains with IDUA-expressing mesenchymal stem cells decreases GAG deposition and improves exploratory behavior.Genetic vaccines and therapy · 2012Article
- Encapsulated engineered myoblasts can cure Hurler syndrome: preclinical experiments in the mouse model.Gene therapy · 2012Article
- Minicircle DNA-based gene therapy coupled with immune modulation permits long-term expression of α-L-iduronidase in mice with mucopolysaccharidosis type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Article
- Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII dogs may be due to increased cytokine expression.Molecular genetics and metabolism · 2010Article
- A self-inactivating gamma-retroviral vector reduces manifestations of mucopolysaccharidosis I in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Systemic correction of storage disease in MPS I NOD/SCID mice using the sleeping beauty transposon system.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency that results in the accumulation of glycosaminoglycans (GAG). Gene therapy can reduce most clinical manifestations, but mice that receive transfer as adults lose expression unless they receive immunosuppression. Increasing liver specificity of transgene expression has reduced immune responses to other genes.
methodsA gamma retroviral vector was generated with a liver-specific human alpha1-antitrypsin promoter and the canine IDUA cDNA inverted relative to the retroviral long-terminal repeat. Adult MPS I mice received the vector intravenously at 6 weeks of age and were assessed for expression via serial serum IDUA assays. Functional testing and organ analysis were performed at 8 months.
resultsThis vector resulted in high specificity of expression in liver, and serum IDUA activity was stable in 90% of animals. Although the average serum IDUA activity was relatively low at 12.6 +/- 8.1 units/ml in mice with stable expression, a relatively high percentage of enzyme contained the mannose 6-phosphorylation necessary for uptake by other cells. At 6.5 months after transduction, most organs had high IDUA activity and normalized GAG levels. There was complete correction of hearing and vision abnormalities and significant improvements in bone, although the aorta was refractory to treatment.
conclusionsStable expression of IDUA in adult MPS I mice can be achieved without immunosuppression by modifying the vector to reduce expression in the spleen. This approach may be effective in patients with MPS I or other lysosomal storage diseases.
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