Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer

X Ye, VM Rivera, P Zoltick, F Cerasoli Jr, MA Schnell… - Science, 1999 - science.org
X Ye, VM Rivera, P Zoltick, F Cerasoli Jr, MA Schnell, G Gao, JV Hughes, M Gilman…
Science, 1999science.org
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 …
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.
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