Patent ID: 7045337

Claim:
A cell comprising: (a.) an orthogonal tRNA synthetase that aminoacylates endogenous tRNAs of the cell with a reduced efficiency as compared to aminoacylation of the endogenous tRNAs by endogenous tRNA synthetases of the cell, and (b.) an orthogonal tRNA that is aminoacylated by the endogenous tRNA synthetases with reduced efficiency as compared to aminoacylation of the endogenous tRNAs by the endogenous tRNA synthetases, wherein said orthogonal tRNA synthetase preferentially aminoacylates said orthogonal tRNA, as compared to the endogenous tRNAs, with an unnatural amino acid in said cell, and wherein the orthogonal tRNA synthetase preferentially aminoacylates aid orthogonal tRNA with an unnatural amino acid, as compared to a natural amino acid, the orthogonal tRNA synthetase having a lower K m for the unnatural amino acid than for the natural amino acid, and wheein said orthogonal tRNA recognizes a selector codon of an mRNA in said cell.