HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Gut epithelial cells as targets for gene therapy of hemophilia.

Abstract
Gut epithelium is an attractive target for gene therapy of hemophilia due to the large number of rapidly dividing cells that should be readily accessible to a wide range of vectors by a noninvasive route of administration. We have performed in vitro tests to determine the suitability of gut epithelial cells for gene transfer, protein synthesis, and secretion of coagulation factors VIII and IX. The results with retroviral vectors indicate that transduced epithelial cells from human, rat, or porcine small or large intestine can synthesize significant amounts of factor VIII or factor IX and that two-thirds or more of the recombinant protein is secreted in a basolateral direction (i.e., away from the lumen and toward underlying capillaries and lymphatics). Furthermore, we have demonstrated that intestinal epithelial cells are susceptible to efficient gene transfer by lipofection and adenovirus vectors. In the case of factor IX, we have produced a high-titer adenovirus vector capable of transducing gut epithelial cells resulting in synthesis of factor IX. The results of our in vitro studies indicate that gene transfer targeting gut epithelium as a new approach to hemophilia gene therapy is rational and merits in vivo studies in hemophilia animal models.
AuthorsJ N Lozier, J R Yankaskas, W J Ramsey, L Chen, H Berschneider, R A Morgan
JournalHuman gene therapy (Hum Gene Ther) Vol. 8 Issue 12 Pg. 1481-90 (Aug 10 1997) ISSN: 1043-0342 [Print] United States
PMID9287148 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Liposomes
  • Recombinant Proteins
  • Factor VIII
  • Factor IX
Topics
  • Adenoviridae (genetics)
  • Animals
  • Cell Line
  • Cell Membrane (metabolism)
  • Epithelial Cells
  • Factor IX (genetics, metabolism)
  • Factor VIII (genetics, metabolism)
  • Gene Transfer Techniques
  • Genetic Therapy (methods)
  • Genetic Vectors (genetics)
  • Hemophilia A (genetics, therapy)
  • Humans
  • Intestines (cytology, virology)
  • Liposomes
  • Rats
  • Recombinant Proteins (genetics, metabolism)
  • Retroviridae (genetics)
  • Transduction, Genetic

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: