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At least first and second forms of a nucleic acid that comprises a control sequence, which forms differ from each other in two or more nucleotides, are reassembled (&/or subjected to one or more directed evolution methods described herein) as described above

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Reduced and alkylated samples were digested with Lysyl endopeptidase (LysC, Wako Chemicals USA) at 1:25 enzyme:protein overnight at room temperature, diluted to 1 M urea with 100 mM EPPS pH 8.1, and digested with trypsin (Promega) at a ratio of 1:15 enzyme:protein for 6 h at 37 C

Currently, there is no approved effective treatment for the disease, leading to an increasing socioeconomic burden and a serious impact on the quality of life of patients (203, 204)