Banaszynski et al. combine genetic manipulation with small-molecule regulation to produce rapid, reversible and tunable regulation of protein expression in vivo. The approach builds on earlier work showing that fusion of a destabilizing domain to a gene of interest confers instability to the expressed protein. Degradation of the protein is then prevented by subsequent addition of the cell-permeable stabilizing ligand, Shield-1, which binds specifically to the destabilizing domains. Three in vivo applications of the technology in mice are described.
- Laura A Banaszynski
- Mark A Sellmyer
- Steve H Thorne