Delivering erythropoietin through genetically engineered cells

Erythropoietin (Epo) is a glycoprotein hormone produced by genetic engineer ing. Many pathologic conditions could benefit from its administration, such as chronic renal failure or hemoglobinopathies. Epo secretion from genetic ally modified tissued could be proposed to patients only if the protocol is low cost and low risk. For that purpose, retroviral vectors and adeno-asso ciated vectors expressing the Epo cDNA were developed. Gene transfer was pe rformed into skeletal muscles. To avoid polycythemia, a tetracycline-regula ted system was used to control the levels of protein secretion in vivo. bet a -thalassemias are among diseases that could benefit from an Epo gene tran sfer. beta -thalassemias are attributable to deficient synthesis of beta -g lobin and accumulation of unpaired alpha -chains. Stimulation of fetal glob in synthesis is one strategy to correct the globin chain imbalance. There i s evidence that Epo could play this role. In a mouse model of beta -thalass emia, an adeno-associated vector expressing the Epo cDNA was injected intra muscularly. Epo was secreted continuously during at least 1 yr. Erythropoie sis was improved in those mice by increasing the synthesis of fetal hemoglo bin.