Inhibitors of ets2-activating molecules for the treatment of inflammatory diseases
AssigneeThe Francis Crick Institute Limited
InventorsJames Christopher Lee, Christophe Jean-Marie Bourges, Christina Therese Stankey
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Abstract
The present invention provides inhibitors of proteins that activate Erythroblast Transformation Specific proto-oncogene (2) (ETS2), and their use in treating or preventing inflammatory and/or autoimmune diseases. The inhibitors are generally MEK inhibitors, HSP90 inhibitors, RAF inhibitors, SRC inhibitors, and/or ERK inhibitors. The invention also encompasses methods of diagnosis and methods of screening for agents that reduce macrophage activation.
Claims17
An inhibitor of a protein that activates Erythroblast Transformation Specific proto-oncogene 2 (ETS2) for use in a method of treating or preventing a disease in a subject, the method comprising administering an inhibitor of a protein that activates Erythroblast Transformation Specific proto-oncogene 2 (ETS2) to the subject, wherein the protein that activates Erythroblast Transformation Specific proto-oncogene 2 (ETS2) is selected from the list consisting of:
- MEK, HSP90, RAF, SRC and ERK, and wherein the disease is an inflammatory and/or autoimmune disease.
A method of screening for agents that reduce macrophage activation, the method comprising:
- (a) contacting a macrophage with a candidate agent;
- and
- (b) determining the expression status of ETS2;
- wherein agents that reduce expression of ETS2 are identified as agents that reduce macrophage activation.
The method of screening for agents according to claim 15, wherein determining the expression status of ETS2 comprises determination of ETS2 mRNA levels or ETS2 protein levels.
A method of screening for candidate genes involved in macrophage activation, the method comprising:
- (a) introducing to a macrophage a CRISPR nuclease system comprising a CRISPR-associated protein (Cas protein) and a guide RNA (gRNA) that specifically binds to the genomic nucleic acid sequence a candidate gene;
- (b) measuring the expression status of ETS2;
- and
- (c) identifying genes as being associated with macrophage activation by comparing the expression status of ETS2 to a reference expression status of ETS2 from a control cell without the CRISPR nuclease system, wherein candidate genes that modulate ETS2 expression status are associated with macrophage activation.
Dependencies are inferred from the claim text.