Chemically inducible split protein actuators
The invention relates to chemically inducible split protein actuators (CISPAs), particularly to their design, manufacture, structure, and uses. The method of engineering CISPAs utilizes ligand-binding proteins or protein domains originating from humans or other organisms, which are rationally split into two fragments that reassemble only in the presence of a cognate ligand, which is typically a small molecule. The designed CISPAs can be used to regulate cellular processes, such as gene expression, as biological sensors, or for other applications.
The designed CISPAs are preferably based on human-derived ligand-binding proteins, which are divided into two fragments that reassemble in the presence of a selected ligand. Thus, the interaction between the split protein fragments is controlled by the presence of the selected ligand. This strategy of CISPA design is inspired by rationally designed split proteins, but unlike previous split proteins, we use ligands that originally bind these intact proteins to induce the reassembly of split fragments. CISPAs can be used as biological actuators or as sensors for in vitro and in vivo detection of selected ligands and respond directly using different reporter output signals or function or change of property.
Our engineered CISPAs are based on human-derived proteins or protein domains, which are suitable for therapeutic applications. The engineering principle for the design of CISPAs is universal and can be used to create novel CISPAs based on almost any ligand-binding domain.
Developed by: Department of Synthetic Biology and Immunology.
Technology readiness level: TRL4.
Status of intellectual property:Patent granted.
Cooperation opportunities: Joint development, intellectual property licensing, or sale.