Chemical Mutagenesis of Human Interferon-β: Construction, Expression in E. coli , and Biological Activity of Sodium Bisulfite-Induced Mutations

A series of modified human interferon-beta (IFN-beta) genes was produced by sodium bisulfite treatment of the IFN-beta gene cloned in M13. A library of mutated sequences was generated from which subgenomic fragments containing one or a small number of coding alterations were isolated and substituted into the IFN-beta gene in an E. coli expression vector. A number of modified genes and their expression products were evaluated. In several instances levels of expression and biological activity profiles are altered compared to the parental gene product. A number of key amino acids can be identified, whose substitutions have marked effects on biological activity of IFN-beta.