Novel Modified β-Interferons: Gene Cloning, Expression, and Biological Activity in Bacterial Extracts

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Abstract
A series of novel, modified interferons based on the structure of human β-interferon have been expressed in Escherichia coli. Modified interferon genes were constructed from sequences derived from the natural β-interferon gene, a synthetic β-interferon gene, or a specific combination of the two. A total of 23 out of the 25 novel interferons exhibited antiviral (AV) and antiproliferative (AP) activity which varied from 3 to 230% and 8 to 490% of the values for β-interferon, respectively. None of the novel interferons had only AV or AP activity, although one had a much reduced ratio of AV/AP activity compared with β-interferon. Substitution of β-interferon amino acids 2–7 or 28–46 resulted in interferons with significantly increased AP activity on Daudi lymphoblastoid cells (four- to fivefold). All the novel interferons except two with modifications in the 82–105 region reacted with a neutralizing β-interferon monoclonal antibody.