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Science 1 January 1999:
Vol. 283. no. 5398, pp. 88 - 91
DOI: 10.1126/science.283.5398.88
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Reports

Regulated Delivery of Therapeutic Proteins After in Vivo Somatic Cell Gene Transfer

Xuehai Ye, Victor M. Rivera, Philip Zoltick, Franklin Cerasoli Jr., Michael A. Schnell, Guang-ping Gao, Joseph V. Hughes, Michael Gilman, James M. Wilson *

Stable delivery of a therapeutic protein under pharmacologic control was achieved through in vivo somatic gene transfer. This system was based on the expression of two chimeric, human-derived proteins that were reconstituted by rapamycin into a transcription factor complex. A mixture of two adeno-associated virus vectors, one expressing the transcription factor chimeras and one containing erythropoietin (Epo) under the control of a promoter responsive to the transcription factor, was injected into skeletal muscle of immune-competent mice. Administration of rapamycin resulted in 200-fold induction of plasma Epo. Stable engraftment of this humanized system in immune-competent mice was achieved for 6 months with similar results for at least 3 months in a rhesus monkey.

X. Ye, P. Zoltick, M. A. Schnell, G.-p. Gao, J. V. Hughes, J. M. Wilson, Institute for Human Gene Therapy and Departments of Molecular and Cellular Engineering and of Medicine, University of Pennsylvania, and the Wistar Institute, Philadelphia, PA 19104, USA. V. M. Rivera, F. Cerasoli Jr., M. Gilman, ARIAD Pharmaceuticals, Cambridge, MA 02139, USA.
*   To whom correspondence should be addressed. E-mail: wilsonjm{at}mail.med.upenn.edu

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