Journal article
In Vivo Treatment of Hemophilia A and Mucopolysaccharidosis Type VII Using Nonprimate Lentiviral Vectors
Molecular therapy, Vol.3(6), pp.850-856
06/2001
DOI: 10.1006/mthe.2001.0325
PMID: 11407898
Abstract
Gene therapy holds great promise for the treatment of a variety of inherited diseases, including hemophilia A and mucopolysaccharidosis type VII (MPS VII). In both these disorders, subnormal levels of replacement protein have therapeutic effects. Thus we hypothesized that transduction of a small proportion of cells by feline immunodeficiency virus (FIV)-based lentiviral vectors might provide sufficient levels of transgene expression for phenotypic correction. We intravenously injected replication-deficient FIV-based vectors encoding either human factor VIII or human β-glucuronidase into factor VIII-deficient or β-glucuronidase-deficient mice, respectively. This route of delivery targeted multiple organs, with the liver as the primary transduction site. In the hemophilia A mice, factor VIII expression persisted for the duration of the experiments (approximately 5 months), and recipient mice survived an otherwise lethal bleeding episode (tail-clipping). In mucopolysaccharidosis type VII mice, substantial β-glucuronidase activity was detected in several tissues and corresponded with marked reduction of lysosomal storage in liver and spleen. These findings indicate that gene transfer with FIV-based lentiviral vectors can permanently introduce transgenes into a sufficient number of hepatocytes for long-term therapeutic effect and suggest potential clinical value of FIV-based lentiviral vectors for treatment of hemophilia A and MPS VII.
Details
- Title: Subtitle
- In Vivo Treatment of Hemophilia A and Mucopolysaccharidosis Type VII Using Nonprimate Lentiviral Vectors
- Creators
- Colleen S Stein - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Yubin Kang - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Sybille L Sauter - Center for Gene Therapy, Chiron Technologies, San Diego, California, 92121Kay Townsend - Center for Gene Therapy, Chiron Technologies, San Diego, California, 92121Patrick Staber - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Todd A Derksen - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Inês Martins - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Jiahua Qian - Department of Biochemistry, University of Minnesota, St. Paul, Minnesota, 55108Beverly L Davidson - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242Paul B McCray - Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.3(6), pp.850-856
- DOI
- 10.1006/mthe.2001.0325
- PMID
- 11407898
- NLM abbreviation
- Mol Ther
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 06/2001
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093495602771
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