Diagnosing and treating cancer cells using T-HR mutants and their targets
OwnerThomas L. Benjamin, Yu Tianinventors
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Abstract
The invention features a novel T-HR mutant virus, new primary cellular targets for DNA tumor viruses, such as Taz, as well as cellular factors, such as Death Inducer with SAP Domain (DIS) polypeptides, that interact with these primary targets. In addition, the invention encompasses DIS nucleic acid and amino acid sequences. The compounds described herein may be used in methods for diagnosing and treating patients having proliferative disorders, such as cancers.
Claims42
A method of determining the presence or absence of an alteration in the genetic material of a cell, said method comprising determining whether a cell can act as a permissive host for the replication and dissemination of a BMD-13 T-HR mutant virus, said BMD-13 T-HR mutant virus being capable of replicating and disseminating in an abnormally proliferating cell and not being capable of replicating and disseminating in a normal cell.
A method of killing an abnormally proliferating cell, said method comprising the steps of:
- (a) contacting an abnormally proliferating cell with a T-HR mutant specific for a cell carrying a Taz, a GAP SH3 binding protein, a nucleolin, a Vesicle Associated Protein 1, or a Death Inducer with SAP Domain alteration;
- and
- (b) allowing said T-HR mutant to lyse said cell.
A BMD-13 T-HR mutant virus.
An isolated nucleic acid encoding a Death Inducer with SAP Domain amino acid sequence, wherein said Death Inducer with SAP Domain amino acid sequence is at least 30% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4 and induces DNA condensation and apoptosis in a mammalian cell.
A method of killing an abnormally proliferating cell, said method comprising the step of contacting said abnormally proliferating cell with a Death Inducer with SAP Domain nucleic acid sequence, wherein said contacting results in the expression of a Death Inducer with SAP Domain polypeptide in said abnormally proliferating cell.
A method of identifying a mammal having or at increased risk of acquiring a proliferative disease, said method comprising the step of determining whether there is a loss of heterozygosity in a Death Inducer with SAP Domain nucleic acid of said mammal, wherein said loss of heterozygosity in a Death Inducer with SAP Domain nucleic acid is indicative of said mammal having, or being at increased risk of acquiring a proliferative disease.
A method of decreasing proliferation of an abnormally proliferating cell, said method comprising the step of contacting said abnormally proliferating cell with a Taz nucleic acid sequence, wherein said contacting results in the expression of a Taz polypeptide having wild-type activity in said abnormally proliferating cell.
A method of decreasing virus replication and dissemination, said method comprising the step of contacting a cell infected with a virus with a T-HR mutant target gene nucleic acid sequence, wherein said contacting results in the expression of a T-HR mutant target gene encoded polypeptide in said cell infected with said virus and prevents said virus from replicating and disseminating.
A knockout mouse comprising a knockout mutation in a genomic Death Inducer with SAP Domain nucleic acid sequence.
A transgenic mouse whose genome comprises a nucleic acid construct including a Death Inducer with SAP Domain nucleic acid sequence, which is operably linked to transcriptional regulatory elements and encodes a Death Inducer with SAP Domain polypeptide.
A method of identifying a compound which modulates cell proliferation, the method comprising:
- a) exposing a cell or a cell extract to a test compound, and
- b) measuring whether said test compound modulates Taz, Nucleolin, Vesicle Associated Protein 1, or Death Inducer with SAP Domain levels, relative to Taz, Nucleolin, Vesicle Associated Protein 1, or Death Inducer with SAP Domain levels in a cell or cell extract not exposed to said test compound.
Dependencies are inferred from the claim text.