Inactivation of dna repair as an anticancer therapy
AssigneePhoremost Limited
InventorsAlberto Bardelli, Giovanni GERMANO, Chris TORRANCE
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Abstract
This invention relates to the modulation of DNA repair and nucleic acid editing mechanisms for use in the treatment of cancer. This invention relates to the inactivation of DNA repair and mechanisms for use in the treatment of cancer. This invention also relates to screening for new anti-cancer agents.
Claims30
A method for treating cancer comprising:
- a) providing i) a subject having cancerous cells, and ii) a modifier of a DNA repair or nucleic acid editing gene, or its protein product;
- and
- b) treating said subject with said modifier wherein said treating reduces the number of cancerous cells in said subject.
A method for screening for anti-cancer compounds comprising
- a) providing cells expressing a DNA repair or nucleic acid editing gene;
- b) incubating said cells in the presence of a test compound;
- and
- c) measuring the rate of DNA or RNA mutation in the presence of a test compound;
- d) wherein an increased rate of DNA or RNA mutation in cells in the presence of a test compound compared to that measured in cells in the absence of a test compound indicates a test compound is an anti-cancer compound.
A method of identifying a patient having a tumour suitable for treatment by immunotherapy comprising:
- a) taking a sample of said tumour,
- b) analysing said sample to determine the sequence of a DNA repair or nucleic acid editing gene, and
- c) comparing the sequence of said DNA repair or nucleic acid editing gene in a tumour sample with the sequence in a non-tumour sample,
- wherein a defect in the sequence of said DNA repair or nucleic acid editing gene in the tumour sample compared to the sequence of said gene in a non-tumour sample is indicative that said patient has a tumour suitable for treatment by immunotherapy.
A method for screening for a modifier of a DNA repair or nucleic acid editing gene, or its protein product, comprising:
- a) providing a construct wherein comprising a simple nucleotide sequence cloned upstream of a reporter coding sequence such that the reporter coding sequence is out of frame;
- b) transfecting cells with the construct of a) in combination with a construct comprising a DNA repair or nucleic acid editing gene;
- c) incubating said cells in the presence of a test compound;
- and
- d) measuring a signal from the reporter construct;
- e) wherein an increase in signal from the reporter construct in the presence of the test compound compared to the signal in the absence of the test compound indicates that the test compound is a modifier of said DNA repair or nucleic acid editing gene, or its protein product.
An inactivator of MLH-1 comprising a CRISPR construct as described herein.
Dependencies are inferred from the claim text.