A method for producing a mammalian cell line that produces at least one therapeutic protein comprising the steps of: a) obtaining a first polynucleotide sequence encoding said at least one protein therapy, b) altering the first polynucleotide sequence to obtain a second polynucleotide sequence, in which the codon adaptation index of the second polynucleotide sequence is greater than that of the first polynucleotide sequence and the first polynucleotide and the second polynucleotide encode the same therapeutic protein. c) transforming at least a first cell of a mammalian cell line with the first polynucleotide sequence of step (a) and a third polynucleotide sequence encoding a selection marker that is capable of providing amplification of the first sequence of polynucleotides within said cell； and transforming at least a second cell of said mammalian cell line with the second polynucleotide sequence of step (b) and a third polynucleotide sequence encoding the selection marker that is capable of providing amplification of the second polynucleotide sequence within said cell, d) culturing at least a first cell of step (c) to create a first cell line comprising a plurality of cells, in a medium containing an increasing concentration or concentration of a selection agent and amplification that (i) inhibits cell growth in said cell line that expresses insufficient levels of the selection marker encoded by the third polynucleotide of step (c), and (ii) increases the number of copies of the gene； culturing at least a second cell of step (c) to create a second cell line comprising a plurality of cells, in a medium containing an increasing concentration or concentration of the selection and amplification agent that (i) inhibits the cell growth in said cell line expressing insufficient levels of the selection marker encoded by the third polynucleotide of step (c), and (ii) increases the number of copies of the gene； and (e) selecting said second cell line once the plateau of pr
