Prodrug activation in cancer cells using molecular switches
The present invention features a novel protein engineering strategy by combining the domains of two independent proteins into a molecular switch. The invention features polypeptides comprising a prodrug activating enzyme and a protein that binds a cancer specific marker, polynucleotides encoding the polypeptides, and molecular switches for converting a prodrug into a toxin, comprising the polypeptides. The invention also features methods for converting a prodrug into a toxin, methods for treating cancer, and methods for making the molecular switches, as well as kits.
1. A polypeptide encoding a molecular switch comprising a cytosine deaminase and a CH1 domain from p300, comprising the amino acid sequence of SEQ ID NO: 1.
2. A polypeptide encoding a molecular switch comprising a cytosine deaminase and a CH1 domain from p300, comprising the amino acid sequence of SEQ ID NO: 2.
3. A molecular switch for converting a prodrug into a toxin, comprising a cytosine deaminase and a CH1 domain corresponding to the amino acid sequence of SEQ ID NO: 1.
4. A molecular switch for converting a prodrug into a toxin, comprising a cytosine deaminase and a CH1 domain corresponding to the amino acid sequence of SEQ ID NO: 2.