Modified human four helical bundle polypeptides and their uses
Modified human four helical bundle (4HB) polypeptides and uses thereof are provided.
1. An isolated nucleic acid comprising at least one N-terminal selector codon that is recognized by an orthogonal translation system and wherein the polynucleotide is translated by the translation system to produce a four helical bundle (4HB) polypeptide selected from the group consisting of human growth hormone, interferon, erythropoietin, and granulocyte cell stimulating factor, and wherein said orthogonal translation system translates the selector codon for a para-acetyl phenylalanine, and wherein the para-acetyl phenylalanine is post-translationally acylated, and wherein the 4HB polypeptide has increased serum half-life as compared to a wild type 4HB polypeptide of the same type.
2. The isolated nucleic acid of claim 1 , wherein the selector codon is selected from the group consisting of an amber codon, ochre codon, opal codon, a unique codon, a rare codon, and a four-base codon.
3. An isolated cell comprising the nucleic acid of claim 1 .
4. The isolated cell of claim 3 , wherein the cell comprises an orthogonal tRNA synthetase or an orthogonal tRNA.