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

Science. 1999 Jan 1;283(5398):88-91. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytomegalovirus / genetics
  • Dependovirus / genetics
  • Erythropoietin / administration & dosage
  • Erythropoietin / blood
  • Erythropoietin / genetics*
  • Female
  • Gene Expression Regulation
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Hematocrit
  • Injections, Intramuscular
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscle, Skeletal
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Sirolimus / pharmacology*
  • Transcription Factors / genetics*

Substances

  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Erythropoietin
  • Sirolimus