HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Persistent delivery of factor IX in mice: gene therapy for hemophilia using implantable microcapsules.

Abstract
Severe hemophilia B is a life-threatening, life long condition caused by absence of or defective coagulation factor IX. Gene therapy could provide an alternative treatment to repeated injection of plasma-derived concentrate or recombinant factor IX. We have previously described the use of implantable microcapsules containing recombinant myoblasts to deliver human factor IX in mice. This study reports the generation of improved myoblast-specific expression vectors. Mouse myoblast clones transfected with the various vectors secreted factor IX in vitro, at rates between 70 and 1000 ng/10(6) cells/day. The recombinant myoblast clones were then encapsulated and implanted into mice. Immunocompetent mice implanted with encapsulated myoblasts had up to 65 ng of factor IX per milliliter in their plasma for up to 14 days, after which antibodies to human factor IX became detectable, and this coincided with decreased factor IX in mouse plasma. In immunodeficient mice, however, factor IX delivery was maintained at a constant level for at least 6 weeks (end of experiment). Interestingly, the highest-secreting myoblast clone in vitro did not deliver the highest level of hFIX in vivo. This discrepancy observed between performance in vitro and in vivo may have important implications for the development of gene therapy protocols based on recombinant cells.
AuthorsG Hortelano, N Xu, A Vandenberg, J Solera, P L Chang, F A Ofosu
JournalHuman gene therapy (Hum Gene Ther) Vol. 10 Issue 8 Pg. 1281-8 (May 20 1999) ISSN: 1043-0342 [Print] United States
PMID10365659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Capsules
  • Drug Carriers
  • Factor IX
Topics
  • Animals
  • Capsules
  • Cell Line
  • Cell Transplantation
  • Drug Carriers
  • Factor IX (genetics, immunology, therapeutic use)
  • Genetic Engineering
  • Genetic Therapy
  • Hemophilia B (therapy)
  • Humans
  • Immunocompetence
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: