Lysosome-Mediated Degradation of Extracellular Proteins
AssigneeWashington University
InventorsGilbert Gallardo, Aisan Farhadi Gharehgheshlaghi, Shreedarshanee Devi Shamulailatpam, Dia Yahng, Sofia Luella Heese
Life of this patent
Estimating the term…
Abstract
Among the various aspects of the present disclosure is the provision of targeting a secreted protein for degradation via the lysosome. Disclosed herein is a composition of a lysosomal degrading chimeric receptor (LDCR). A method to treat diseases by targeting a secreted protein to the lysosome using LDCRs is also disclosed.
Claims19
A composition for degrading a target protein in a patient, the composition comprising a lysosomal degrading chimeric receptor (LDCR), the LDCR comprising:
- a. an engineered mannose 6-phosphate receptor (MPR), the engineered MPR comprising an MPR with a targeting moiety fused at least one of a transmembrane domain, a cytoplasmic domain, and any combination thereof;
- or
- b. an engineered asialoglycoprotein receptor (ASGPR), the engineered ASGPR comprising an ASGPR with the targeting moiety fused at least one of an extracellular stalk region and a carbohydrate recognition binding domain, and any combination thereof;
- wherein the targeting moiety is configured to bind to the target protein.
A method of treating a disease or disorder in a patient by targeting a secreted protein for degradation via a lysosome, the method comprising administering a composition comprising a therapeutically effective amount of a lysosomal degrading chimeric receptor (LDCR) to the patient the LDCR comprising:
- a. an engineered mannose 6-phosphate receptor (MPR), the engineered MPR comprising an MPR with a targeting moiety fused at least one of a transmembrane domain, a cytoplasmic domain, and any combination thereof;
- or
- b. an engineered asialoglycoprotein receptor (ASGPR), the engineered ASGPR comprising an ASGPR with the targeting moiety fused at least one of an extracellular stalk region and a carbohydrate recognition binding domain, and any combination thereof;
- wherein the targeting moiety is configured to bind to the target protein.
Dependencies are inferred from the claim text.