Nucleic acid encoding rrm2 subunit of ribonucleotide reductase to resist degradation
AssigneeUniversity of Washington
InventorsMichael REGNIER, Charles E. MURRY, Xuan GUAN
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Abstract
Provided herein are isolated nucleic acids that encode a stable form of Rrm2 for the use of increasing the intracellular Rrm2 protein levels and cytosolic 2-deoxy-ATP (dATP) levels. Further provided herein are methods for treating a cardiac disease or disorder, e.g., myocardial infarction or myocardial ischemia, by administering the isolated nucleic acids, a polypeptide encoded by the isolated nucleic acids, or composition comprising the isolated nucleic acids to a subject in need thereof.
Claims20
A method of treating a patient with a cardiac disease or disorder, the method comprising administering to a subject in need thereof a composition comprising a nucleic acid molecule encoding a mutant Rrm2 polypeptide, wherein the nucleic acid molecule comprises a mutated version of SEQ ID NO:
- 3 or SEQ ID NO:
- 5, the version having at least a mutation of a nucleotide selected from the group consisting of:
- positions 88-96, 97-99, and 145-153 of SEQ ID NO:
- 3 or SEQ ID NO:
- 5,
- wherein the encoded mutant Rrm2 polypeptide comprises a mutation in a ubiquitin-binding degron relative to a wild-type Rrm2 polypeptide, wherein the ubiquitin-binding degron is encoded by wild-type nucleotides 88-96, 97-99, and/or 145-153 of SEQ ID NO:
- 3 or SEQ ID NO:
- 5,
- wherein the mutation in the ubiquitin-binding degron increases the intracellular stability of the mutant Rrm2 polypeptide compared to the wild-type, and
- wherein the nucleic acid molecule is operably linked to a sequence that permits expression of the encoded polypeptide in a cell.
A method of treating a patient with a cardiac disease or disorder, the method comprising administering to a subject in need thereof a composition comprising a nucleic acid molecule encoding a mutant Rrm2 polypeptide, wherein the nucleic acid molecule has a sequence selected from SEQ ID NO:
- 16-20,
- wherein the nucleic acid molecule is operably linked to a sequence that permits expression of the encoded polypeptide in a cell.
A method of treating a patient with a cardiac disease or disorder, the method comprising:
- a) diagnosing a subject as having a cardiac disease or disorder or receiving the results of an assay that diagnoses a subject as having a cardiac disease or disorder;
- b) administering to a subject in need thereof a composition comprising a nucleic acid molecule encoding a mutant Rrm2 polypeptide, wherein the nucleic acid molecule comprises a mutated version of SEQ ID NO:
- 3 or SEQ ID NO:
- 5, the version having at least a mutation of a nucleotide selected from the group consisting of:
- positions 88-96, 97-99, and 145-153 of SEQ ID NO:
- 3 or SEQ ID NO:
- 5,
- wherein the encoded mutant Rrm2 polypeptide comprises a mutation in a ubiquitin-binding degron relative to a wild-type Rrm2 polypeptide, wherein the ubiquitin-binding degron is encoded by wild-type nucleotides 88-96, 97-99, and/or 145-153 of SEQ ID NO:
- 3 or SEQ ID NO:
- 5,
- wherein the mutation in the ubiquitin-binding degron increases the intracellular stability of the mutant Rrm2 polypeptide compared to the wild-type, and
- wherein the nucleic acid molecule is operably linked to a sequence that permits expression of the encoded polypeptide in a cell.
Dependencies are inferred from the claim text.