A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension.

Détails

ID Serval
serval:BIB_0E9AF081690C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension.
Périodique
Human Gene Therapy
Auteur(s)
Rinsch C., Régulier E., Déglon N., Dalle B., Beuzard Y., Aebischer P.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Statut éditorial
Publié
Date de publication
1997
Volume
8
Numéro
16
Pages
1881-1889
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Current therapy for several forms of anemia involves a weekly regime of multiple subcutaneous injections of recombinant human erythropoietin (hEpo). In an effort to provide a physiologically regulated administration of erythropoietin, we are developing cell lines genetically engineered to release hEpo as a function of oxygen tension. C2C12 cells were transfected using a vector containing the hEpo cDNA driven by the hypoxia-responsive promoter to the murine phosphoglycerate kinase gene. In vitro, these cells showed a threefold increase in hEpo secretion as oxygen levels were shifted from 21% to 1.3% oxygen. To test in vivo response, C2C12-hEpo cells were encapsulated in a microporous membrane and implanted subcutaneously on the dorsal flank of DBA/2J mice. On average, serum hEpo levels in animals exposed to 7% oxygen were two-fold higher than values seen in their control counterparts kept at 21% oxygen. Similar studies employing rats confirmed that hEpo delivery is regulated as a function of oxygen tension. These results suggest the feasibility of developing an oxygen-regulated, encapsulated cell-based system for hEpo delivery.
Mots-clé
Anemia/therapy, Animals, Anoxia/metabolism, Cells, Cultured, DNA-Binding Proteins/genetics, Drug Compounding, Erythropoietin, Recombinant/blood, Erythropoietin, Recombinant/genetics, Gene Expression Regulation, Gene Therapy/methods, Histocytochemistry, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Mice, Inbred DBA, Nuclear Proteins/genetics, Oxygen/blood, Oxygen/physiology, Partial Pressure, Phosphoglycerate Kinase/genetics, Plasmids/genetics, Promoter Regions, Genetic/genetics, Rats, Rats, Inbred F344, Transcription Factors, Transgenes
Pubmed
Web of science
Création de la notice
13/12/2011 17:41
Dernière modification de la notice
20/08/2019 13:35
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