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US 2025/0019672 A1Published application
Destabilising domains for conditionally stabilising a protein
AssigneeBraingene AB
InventorsMauno Vihinen, Deniz Kirik
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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.
Claims21
1-37. (canceled)
A fusion polypeptide comprising:
- i) a mutant dihydrofolate reductase (DHFR) polypeptide comprising or consisting of an amino acid sequence 90% or greater identity to the amino acid sequence of SEQ ID NO:
- 1 or the amino acid sequence of SEQ ID NO:
- 2 and comprising a mutation in at least one of the following positions:
- W133, Y100, and/or M42, and 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.
6 more elements
Dependencies are inferred from the claim text.