LONG-TERM CONTROL OF ERYTHROPOIETIN SECRETION BY DOXYCYCLINE IN MICE TRANSPLANTED WITH ENGINEERED PRIMARY MYOBLASTS

We investigated tetracycline regulation of gene expression in an exper imental model relevant to gene therapy. Mouse primary myogenic cells w ere engineered for doxycycline-inducible and skeletal muscle-specific expression of the mouse erythropoietin (Epo) cDNA by using two retrovi rus vectors. Gene expression increased 200 fold in response to both my ogenic cell differentiation and doxycycline stimulation. After transpl antation of transduced cells into mouse skeletal muscles, Epo secretio n could be iteratively switched on and off over a five-month period, d epending on the presence or the absence of doxycycline in the drinking water. We conclude that tetracycline regulation provides a suitable c ontrol system for adjusting the delivery of therapeutic proteins from engineered tissues over long periods of time.