title: Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer.
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.
authors.affiliation: Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: V M
authors.initials: VM
authors.lastname: Rivera
authors.forename: P
authors.initials: P
authors.lastname: Zoltick
authors.forename: F
authors.initials: F
authors.lastname: Cerasoli
authors.forename: M A
authors.initials: MA
authors.lastname: Schnell
authors.forename: G
authors.initials: G
authors.lastname: Gao
authors.forename: J V
authors.initials: JV
authors.lastname: Hughes
authors.forename: M
authors.initials: M
authors.lastname: Gilman
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006400:Hematocrit; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018482:Muscle, Skeletal; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D020123:Sirolimus / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D004921:Erythropoietin; D020123:Sirolimus