Targeted epigenetic therapy against distal regulatory element of tgfb2 expression
AssigneeThe Johns Hopkins University
InventorsHarry C. Dietz, Joseph Shin
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Abstract
The instant disclosure provides methods and compositions for the diagnosis, treatment and prevention of a TGFβ2-associated disease, disorder and/or condition, including, e.g., Scleroderma, other fibrotic disease, grade 4 glioblastoma (GBM) and/or Primary Open-Angle Glaucoma (POAG). The disclosure further provides pharmaceutical compositions and kits for the diagnosis, treatment and prevention of TGFβ2-associated diseases, disorders and/or conditions.
Claims25
A method for treating a subject having or at risk of developing a transforming growth factor β2-associated disease, disorder and/or condition comprising:
- administering to the subject an effective amount of one or more agents that modulate transforming growth factor β2 (TGFβ2) expression by targeting an enhancer sequence distal to a TGFβ2 locus,
- thereby treating the subject.
9-12. (canceled)
A method of identifying a candidate agent for treating a transforming growth factor β2-associated disease, disorder and/or condition comprising:
- contacting a cell comprising an enhancer sequence which modulates transforming growth factor β2 (TGFβ2) expression with a candidate agent;
- and,
- comparing expression levels of TGFβ2 with a normal control;
- wherein the candidate agent inhibits of TGFβ2 expression.
18-20. (canceled)
25-27. (canceled)
A method of treating a subject having transforming growth factor β2-associated disease, disorder and/or condition, comprising:
- administering to the subject an isolated nucleic acid sequence encoding a gene-editing complex comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease and at least one guide RNA (gRNA), the gRNA being complementary to a target sequence in an enhancer distal to a transforming growth factor β2 (TGFβ2), wherein the gene editing complex normalizes expression of TGFβ2,
- thereby treating the subject.
30-33. (canceled)
An isolated nucleic acid encoding:
- a guide nucleic acid, wherein the guide nucleic acid comprises a targeting nucleotide sequence directed to one or more target sequences in an enhancer distal to a transforming growth factor β2 (TGFβ2);
- a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease/Cas (CRISPR/Cas), comprising CRISPR/Cas tethered or conjugated to one or more modulators associated with TGFβ2 expression.
35-37. (canceled)
Dependencies are inferred from the claim text.