Details

Autor(en) / Beteiligte

• Stein, Colleen S.
• Kang, Yubin
• Sauter, Sybille L.
• Townsend, Kay
• Staber, Patrick
• Derksen, Todd A.
• Martins, Inês
• Qian, Jiahua
• Davidson, Beverly L.
• McCray, Paul B.

Titel

In Vivo Treatment of Hemophilia A and Mucopolysaccharidosis Type VII Using Nonprimate Lentiviral Vectors

Ist Teil von

• Molecular therapy, 2001-06, Vol.3 (6), p.850-856

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2001

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.