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AssigneeThe Regents of the University of California
InventorsTaylor Hanh NGUYEN, Galen DODS, Hana EL-SAMAD, Andrew H. NG
Estimating the term…
Provided herein is a molecular switch and a variety of feedback and feed-forward circuits that employ a split protein (e.g., a split transcription factor) and monomers from designed heterodimers In some embodiments, the cell may contain a first polypeptide comprising a first part of a split protein and a monomer of a designed heterodimer; (b) a second polypeptide comprising a second part of a split protein and a monomer of a designed heterodimer; and (c) a third polypeptide comprising a monomer of a designed heterodimer, not containing the first or second parts of the split protein. In these embodiments, (a) and (b) bind to each other, and (c) binds to (a) or (b), thereby inactivating the reconstituted split protein. Expression of (c) is regulated by the activity of the reconstituted split protein. Various circuits are also provided.
A cell comprising a molecular switch comprising:
A cell comprising a feedback circuit comprising:
A cell comprising a feedforward circuit comprising:
The cell of any prior claim, wherein the third polypeptide comprises a degron.
The cell of any prior claim, wherein the monomers are selected from SEQ ID NOS:
The cell of any prior claim, wherein the reconstituted split protein is transcription factor, enzyme, kinase or chimeric antigen receptor.
The cell of prior claim, wherein the split protein is a split transcription factor, the cell comprises an expression cassette comprising a promoter and a coding sequence that are operably linked, and transcription of the coding sequence is activated by the split transcription factor.
The cell of any prior claim, wherein the cell is an immune cell.
A method comprising:
Dependencies are inferred from the claim text.