Materials and methods for extracellular vessicle-associated diseases
AssigneeThe Brigham and Women's Hospital, Inc.
InventorsShinsuke ITO, Elena AIKAWA, Masanori AIKAWA
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Abstract
Sortilin is a sorting receptor that directs target proteins to the secretary or endocytic compartments of cells that is found in both extracellular vesicles and cells. Provided herein are methods and compositions for decreasing or inhibiting trafficking of sortilin to an extracellular vesicle, for example by inhibiting the formation of intermolecular sortilin dimers.
Claims21
A method for inhibiting or reducing trafficking of sortilin to an extracellular vesicle (EV) from a cell, the method comprising inhibiting covalent intermolecular dimerization of sortilin in the cell.
A method of treating an extracellular vesicle associated disease in subject, comprising:
- inhibiting covalent intermolecular dimerization of sortilin in a cell in a subject in need thereof.
-28. (canceled)
A method for identifying a test agent that modulates dimerization of sortilin, the method comprising:
- (i) contacting a cell with a test agent, wherein the cell expresses a first sortilin polypeptide comprising a first label, and a second sortilin polypeptide comprising a second label;
- (ii) detecting a contact level between the first and second sortilin polypeptide expressed in the cell,
- wherein a change in contact level relative to a control or reference level indicates the agent modulates dimerization of sortilin.
-37. (canceled)
A method for preparing dimeric soluble sortilin, the method comprising:
- (i) expressing a sortilin polypeptide comprising a first label in an extracellular domain from a cell;
- (ii) purifying the expressed sortilin polypeptide via affinity purification using a ligand capable of binding with the first label.
Dependencies are inferred from the claim text.