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US 2021/0062227 A1Published application
Chimeric Proteins and Methods of Regulating Gene Expression
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsLei S. Qi, P.C. Dave P. Dingal
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Abstract
The present disclosure provides systems, compositions and methods for regulating expression of a target polynucleotide in a cell. The systems, compositions and methods comprise a chimeric receptor polypeptide comprising a G-protein coupled receptor (GPCR) or a fragment thereof, a chimeric adaptor polypeptide, at least one actuator moiety and a cleavage moiety.
Claims30
A system for regulating expression of a target polynucleotide in a cell, the system comprising:
- (a) a chimeric receptor polypeptide (receptor) comprising a transmembrane receptor or a fragment thereof, that undergoes a receptor modification including a conformational change or chemical modification upon binding to its ligand, wherein the receptor comprises a cleavage moiety that cleaves a cleavage recognition site;
- and
- (b) a chimeric adaptor polypeptide (adaptor) that binds the receptor in response to the receptor modification, wherein the adaptor comprises a gene modulating polypeptide (GMP) comprising an actuator moiety linked to the cleavage recognition site, and wherein the adaptor does not bind any extracellular ligand;
- wherein the target polynucleotide encodes a protein selected from the group consisting of Jun, Fos, and IL-12, and
- wherein the receptor is activatable upon binding of the receptor to the ligand to recruit the adaptor to the receptor, and wherein the receptor releases the actuator moiety from the GMP of the recruited adaptor by action of the cleavage moiety at the cleavage recognition site, to effect regulating expression of the target polynucleotide in the cell.
2 more elements
A method for regulating expression of a target polynucleotide in a cell, the method comprising:
- (a) contacting a ligand to a chimeric transmembrane receptor polypeptide (receptor) comprising a cleavage moiety, wherein the receptor is modified upon contacting to the ligand, and wherein the receptor modification comprises a conformational change or a chemical modification;
- (b) binding a chimeric adaptor polypeptide (adaptor) comprising a gene modulating polypeptide (GMP) to the receptor in response to the receptor modification, wherein the GMP comprises an actuator moiety linked to a cleavage recognition site, wherein the receptor is activatable upon binding of the receptor to the ligand to recruit the adaptor to the receptor, and wherein the adaptor does not bind any extracellular ligand;
- and
- (c) releasing the actuator moiety from the GMP of the recruited adaptor by action of the cleavage moiety at the cleavage recognition site, to effect regulating expression of the target polynucleotide in the cell, wherein the target polynucleotide encodes a protein selected from the group consisting of Jun, Fos, and IL-12.
1 more element
Dependencies are inferred from the claim text.