Regulated Delivery of Therapeutic Proteins After in Vivo Somatic Cell Gene Transfer
- 1 January 1999
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 283 (5398) , 88-91
- https://doi.org/10.1126/science.283.5398.88
Abstract
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.Keywords
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