In vivo treatment of hemophilia A and mucopolysaccharidosis type VII using nonprimate lentiviral vectors

Mol Ther. 2001 Jun;3(6):850-6. doi: 10.1006/mthe.2001.0325.


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 beta-glucuronidase into factor VIII-deficient or beta-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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA Primers / chemistry
  • Defective Viruses
  • Disease Models, Animal
  • Factor VIII / genetics*
  • Factor VIII / metabolism
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors*
  • Glucuronidase / deficiency
  • Glucuronidase / genetics*
  • Glucuronidase / metabolism
  • Hemophilia A / metabolism
  • Hemophilia A / pathology
  • Hemophilia A / therapy*
  • Immunodeficiency Virus, Feline / genetics*
  • Injections, Intravenous
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucopolysaccharidosis VII / metabolism
  • Mucopolysaccharidosis VII / pathology
  • Mucopolysaccharidosis VII / therapy*
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA Primers
  • Factor VIII
  • Glucuronidase