Method and apparatus for optimizing nucleotide sequences for protein expression

摘要

Computer optimization of a nucleotide sequence for a protein comprises generating a test sequence; establishing positions corresponding to codons to be optimized; generating further test sequences by replacing one or more of these codons with another codon for the same amino acid; evaluating the test sequences with a quality function to determine the optimum sequence; establishing codons of the optimum sequence as success codons; and iterating the above steps without changing the success codons. Computer optimization of a nucleotide sequence for expression of a protein comprising N amino acids comprises generating a test sequence of n codons corresponding to n contiguous amino acids of the protein sequence, where n is =N; establishing m positions corresponding to codons to be optimized, where m is = n and less than N; generating one or more further test sequences by replacing one or more of the m codons with another codon encoding the same amino acid; evaluating the test sequences with a quality function to determine the optimum sequence; establishing p codons of the optimum sequence as success codons, where p is =m; and iterating the above steps without changing the success codons. Independent claims are also included for: (1) computer apparatus for optimization of a nucleotide sequence for expression of a protein, comprising means for performing the above steps; (2) computer program for performing the above method; (3) data carrier on which the above program is stored in computer-readable form; (4) nucleic acid (I) comprising a protein-encoding nucleotide sequence produced by synthesizing the sequence optimized as above; (5) nucleic acid (II) comprising one of four defined nucleotide sequences; (6) vector containing (I) or (II); (7) cells containing the vector or (I) or (II); (8) organism comprising at least one cell as above.