Delivering erythropoietin through genetically engineered cells.
Erythropoietin (Epo) is a glycoprotein hormone produced by genetic engineering. Many pathologic conditions could benefit from its administration, such as chronic renal failure or hemoglobinopathies. Epo secretion from genetically modified tissued could be proposed to patients only if the protocol is low cost and low risk. For that purpose, retroviral vectors and adeno-associated vectors expressing the Epo cDNA were developed. Gene transfer was performed into skeletal muscles. To avoid polycythemia, a tetracycline-regulated system was used to control the levels of protein secretion in vivo. beta-thalassemias are among diseases that could benefit from an Epo gene transfer. beta-thalassemias are attributable to deficient synthesis of beta-globin and accumulation of unpaired alpha-chains. Stimulation of fetal globin synthesis is one strategy to correct the globin chain imbalance. There is evidence that Epo could play this role. In a mouse model of beta-thalassemia, an adeno-associated vector expressing the Epo cDNA was injected intramuscularly. Epo was secreted continuously during at least 1 yr. Erythropoiesis was improved in those mice by increasing the synthesis of fetal hemoglobin.
Bohl
D
D
Retrovirus and Genetic Transfer Laboratory, CNRS ERS 572, Pasteur Institute, Paris, France. dbohl@pasteur.fr
Heard
J M
JM
D000818:Animals; D017690:Cell Transplantation; D004921:Erythropoietin / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D017086:beta-Thalassemia / Q000628:therapy
D004921:Erythropoietin