Bipartite T-cell factor (Tcf)-responsive promoter
OwnerMien-Chie Hung, Ka Yin Kwong +1inventors
InventorsMien-Chie Hung, Ka Yin Kwong, Yiyu Zou
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Abstract
The present invention is directed to methods and compositions for cancer therapy, particularly cancers resulting from a defective Wnt/β-catenin signaling pathway. In specific embodiments, a T-cell factor (Tcf)-responsive promoter regulating expression of a therapeutic gene is administered to an individual having the cancer. In a specific embodiment, the Tcf-responsive promoter comprises a minimal CMV promoter and is present on an adenovirus vector. The promoter regulates expression of a therapeutic gene.
Claims64
A viral vector, comprising:
- a β-catenin/Tcf-responsive promoter construct comprising:
- a first promoter region having at least one copy of a Tcf/LEF-1 binding site, operatively linked to;
- a second promoter region;
- and
- a nucleic acid sequence encoding an amino acid sequence of interest, wherein the first and second promoter regions are operatively linked to the target nucleic acid sequence.
A nucleic acid segment comprising β-catenin/Tcf-responsive promoter construct comprising a first promoter region having a Tcf/LEF-1 binding site operatively linked to a second promoter, said second promoter being a minimal CMV promoter.
A method of treating an individual with cancer, comprising administering to the individual a vector, said vector comprising:
- a β-catenin/Tcf-responsive promoter construct comprising:
- a first promoter region having at least one copy of a Tcf/LEF-1 binding site, operatively linked to;
- a second promoter region;
- and
- a nucleic acid sequence encoding a therapeutic polypeptide, wherein the first and second promoter regions are operatively linked to the nucleic acid sequence.
A method of treating colon cancer in an individual, comprising administering to the individual an adenoviral vector comprising:
- a β-catenin/Tcf-responsive promoter construct comprising:
- a first promoter region having three copies of a Tcf/LEF-1 binding site, operatively linked to;
- a minimal CMV promoter;
- and
- a nucleic acid sequence encoding thymidine kinase, wherein the first and second promoter regions are operatively linked to the nucleic acid sequence.
A method of screening for a modifier of β-catenin activity, comprising:
- providing a β-catenin/Tcf-responsive promoter construct comprising:
- a first promoter region having at least one copy of a Tcf/LEF-1 binding site, operatively linked to;
- a second promoter;
- and
- a reporter nucleic acid sequence, wherein the first and second promoter regions are operatively linked to the reporter nucleic acid sequence;
- introducing to the vector a test compound;
- and
- assaying for a change associated with the reporter nucleic acid sequence, wherein when said change occurs, said test compound is said modifier.
Dependencies are inferred from the claim text.