A Method to Regulate Protein Function in Living Cells Using Small Molecules

Applications

• Drug discovery
• validate targets by assessing effects of controlled, transient destabilization of protein
• study side effects of pharmacologic agent
• Transgenic animals
• Research Kits - to study:
• effects of protein knock-outs (either partial or complete knock-out)
• role of protein during discrete physiological or developmental event
• Stem Cell Therapy - control activity of a fusion protein to:
• differentiate progenitor cells
• reverse differentiation of somatic cells

Advantages

• Specific - stabilizing ligand binds fusion protein and does not affect other cell functions
• Fast - upon withdrawal of the stabilizing ligand, proteins are totally degraded in 2-4 hours.
• Tunable- action of ligand is dose-dependent, enabling studies of proteins whose function depends on its intracellular concentration
• Reversible
• Versatile - system has been demonstrated with 18 different proteins, including:
• cytosolic
• nuclear
• membrane-bound (both single-pass and GPCRs)

Publications

• Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell. 2006 Sept. 8;126(5):995-1004.

Web Site

Wandless Lab

Patents

• Published Application: 0-
• Published Application: 20090215169
• Published Application: 20120178168
• Issued: 8,173,792 (USA)
• Issued: 9,487,787 (USA)