A method for regulating expression of a tet operator-linked
gene in a
cell of a subject is disclosed. In one embodiment, the method involves introducing into the
cell a
nucleic acid molecule encoding a
tetracycline-controllable transactivator (tTA), the tTA comprising a Tet
repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a
tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the
cell from the subject, introducing into the cell a first
nucleic acid molecule which operatively links a
gene to at least one tet operator sequence, introducing into the cell a second
nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a
tetracycline, or analogue thereof, in the subject. The first and second
nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.