Oral drug turns on gene transcription

Abstract

Researchers at a biotech firm have for the first time used rapamycin, an oral drug, to control production of a therapeutic protein by engineered human cells in mice. Rapamycin acts as a dimerizer to link two other proteins made by the engineered cells. When bound together, the two proteins form an active transcription factor that induces the cells to express sustained and therapeutic levels of human growth hormone (hGH). Scientific director Michael Gilman and coworkers at Ariad Gene Therapeutics, Cambridge, Mass., controlled hGH production with rapamycin in a dosedependent manner in mice implanted with engineered cells containing the hGH gene and two regulatory genes for transcription factor proteins [Nature Medicine, 2,1028 (1996)]. The two regulatory proteins had been modified to include recognition sites for rapamycin. When rapamycin was given to the mice, the two proteins were spliced together in the engineered cells—forming a complex that bound to the cells' DNA, activated the hGH gene, and ...