Modified interferon beta polypeptides and their uses

1. An isolated nucleic acid comprising a polynucleotide that encodes an interferon beta polypeptide comprising an amino acid sequence SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 4, wherein the polynucleotide comprises an amber selector codon and wherein the amber selector codon selectively incorporates a non-naturally encoded amino acid at amino acid position 36 of the polypeptide sequence of SEQ ID NO: 1 or SEQ ID NO: 3, or the corresponding amino acid position in SEQ ID NO: 4, and wherein the non-naturally encoded amino acid has a ketone moiety.

2. A cell comprising the nucleic acid of claim 1 .

3. The cell of claim 2 , wherein the cell comprises an orthogonal tRNA synthetase or an orthogonal tRNA.

4. A method of making a IFN beta polypeptide comprising a non-naturally encoded amino acid, the method comprising, culturing cells comprising a polynucleotide or polynucleotides encoding a IFN beta polypeptide comprising an amber selector codon wherein the amber codon is selective for a non-naturally encoded amino acid with a ketone functional group, an orthogonal RNA synthetase and an orthogonal tRNA under conditions to permit expression of the IFN beta polypeptide comprising a non-naturally encoded amino acid at amino acid position 36 of polypeptide sequence SEQ ID NO: 1 or the corresponding amino acids in SEQ ID NOs: 3 or 4; and purifying the IFN beta polypeptide.