Research Project
2271627
DESCRIPTION (Adapted from applicant's abstract): This application describes construction of a vector for a gene therapy that can be incorporated into somatic cells in vivo and then regulated by administration of an oral, non- toxic, and widely bioavailable drug. The "gene switch" is based on a derived mutant of the progesterone receptor that is activated by progesterone antagonists but is not activated by progesterone agonists or other steroids. This mutant will be recombined with DNA binding sequences that recognize a unique element not found in human cells. The gene encoding the gene switch under the control of a constitutive promoter will be introduced into cells with the therapeutic gene and will be regulated specifically and selectively by anti- progestins at low levels that will exert no anti-progesterone effect. The vector will be validated using a tyrosine hydroxylase gene controlled by the gene switch. Cells containing these genes will be used to treat an animal model of Parkinson's disease. This will serve as a model for vectors that may be used to treat complex, neurodegenerative diseases where tight control of gene expression will be important.
