Multipartite signaling proteins and uses thereof
First Claim
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1. An isolated non-natural cell, comprising:
- (a) a first exogenous polynucleotide encoding a first fusion protein comprising a first multimerization domain, a first transmembrane domain, and an actuator domain, wherein the first multimerization domain localizes extracellularly when the first fusion protein is expressed; and
(b) a second exogenous polynucleotide encoding a second fusion protein comprising a secretion signal;
a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand;
a second multimerization domain; and
a second transmembrane domain, wherein the binding domain and the second multimerization domain localizes extracellularly when expressed;
wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second fusion proteins.
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Abstract
Nucleic acids that encode chemically-inducible fusion proteins, vectors that contain nucleic acids that encode chemically-inducible fusion proteins, chemically-inducible fusion proteins, chemically-inducible fusion protein complexes, and non-natural cells that are modified to express chemically-inducible fusion proteins to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.
19 Citations
27 Claims
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1. An isolated non-natural cell, comprising:
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(a) a first exogenous polynucleotide encoding a first fusion protein comprising a first multimerization domain, a first transmembrane domain, and an actuator domain, wherein the first multimerization domain localizes extracellularly when the first fusion protein is expressed; and (b) a second exogenous polynucleotide encoding a second fusion protein comprising a secretion signal;
a binding domain that comprises a single chain antibody, a receptor ectodomain, or a ligand;
a second multimerization domain; and
a second transmembrane domain, wherein the binding domain and the second multimerization domain localizes extracellularly when expressed;wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second fusion proteins. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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Specification