FK506-BASED REGULATION OF BIOLOGICAL EVENTS

This invention provides methods and materials for making and using genetically engineered cells which are responsive to the presence of an FKBP/CAB ligand or a cyclophilin/CAB ligand. The invention relies upon the introduction into cells of recombinant DNAs encoding fusion proteins which are capable of forming a complex with each other in the presence of ligand. One of the fusion proteins contains a calcineurin A/calcineurin B domain (CAB) and at least one heterologous protein domain. The second fusion protein contains a domain derived from an FKBP protein which is capable of binding to an FKBP/CAB ligand and forming a complex with a CAB-containing protein. The second fusion protein may alternatively contain a cyclophilin domain which is capable of binding cyclosporin or other cyclophilin/CAB ligand and forming a complex with a CAB-containing protein. The second fusion protein also contains at least one heterologous domain. Materials and methods are disclosed for regulation of biological events such as target gene transcription and growth, proliferation or differentiation of engineered cells. On décrit des matières et des procédés qui permettent de réguler des événements biologiques tels que la transcription de gènes cibles et la croissance, la prolifération ou la différenciation de cellules génétiquement modifiées.