FIELD: biotechnology.
SUBSTANCE: invention is related specifically to therapeutic proteins based on the human protein Lefty A, and can be used in medicine to prevent or treat a neuromuscular disease. A variant of the human Lefty A protein was constructed containing the amino acid sequence L22 to P366 of SEQ ID NO: 131 with a substitution of one or more amino acid residues at processing sites selected from the group consisting of R74G, R77G or R77V, R132G and R135G; and replacing one or more amino acid residues in the propeptide domain selected from the group consisting of E24G, S38K, V42T, K50E, A55T, V63A and R66Q. A fusion protein with Fc or albumin was also obtained based on this human Lefty A variant.
EFFECT: invention provides for the production of variant proteins with the activity of the human Lefty A protein, which have better stability than the native human Lefty A protein and thus are expressed at high levels and produced in high yield in CHO cells.
18 cl, 23 dwg, 16 tbl, 18 ex
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Authors
Dates
2023-04-04—Published
2019-12-17—Filed