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US 12,534,711 B2Granted
Destabilising domains for conditionally stabilising a protein
AssigneeBraingene AB
InventorsMauno Vihinen, Deniz Kirik
Life of this patent
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Abstract
The present disclosure relates to mutant polypeptides derived from Escherichia coli dihydrofolate reductase (DHFR) which can be fused to a polypeptide of interest for efficient conditional modulation of its activity. Also disclosed are polynucleotides encoding such mutant polypeptides, vectors comprising such polynucleotides, and the use of such polypeptides, polynucleotides and vectors for treating a disorder.
Claims20
A fusion polypeptide comprising:
- i) a mutant dihydrofolate reductase (DHFR) polypeptide selected from the group consisting of:
- a) a mutant DHFR polypeptide comprising the amino acid sequence of SEQ ID NO:
- 1 or SEQ ID NO:
- 2 with the exception of a single mutation selected from the group consisting of Y100E, M42A, and M42G, and
- b) a mutant DHFR polypeptide comprising an amino acid sequence having 90% or greater amino sequence identity to the amino acid sequence of SEQ ID NO:
- 1 or having 90% or greater amino acid sequence identity to the amino acid sequence of SEQ ID NO:
- 2 and comprising a mutation in position W133,
- wherein the mutant DHFR polypeptide is capable of binding to a DHFR inhibitor, and
- ii) a polypeptide of interest,
- wherein the mutant DHFR polypeptide is operatively linked to the polypeptide of interest,
- wherein in the absence of said DHFR inhibitor said fusion polypeptide is destabilized as compared to a DHFR polypeptide consisting of the amino acid sequence of SEQ ID NO:
- 1, and wherein in the presence of said DHFR inhibitor, said fusion polypeptide is stabilized.
9 more elements
Dependencies are inferred from the claim text.