Bioengineering: alpha 1-proteinase inhibitor site-specific mutagenesis. The prospect for improving the inhibitor.

Abstract

alpha 1-Proteinase inhibitor (alpha 1-PI) augmentation therapy has been licensed for treatment of alpha 1-PI-deficient individuals with pulmonary emphysema. The currently available product is purified from pooled human plasma. To obtain larger amounts of protein free from possible unknown plasma contaminants, human alpha 1-PI has been produced by recombinant DNA. Since wild-type alpha 1-PI is susceptible to oxidative impairment, several alpha 1-PI variants in which the active site oxidation-sensitive residue is replaced by inert residues have been constructed. This article is aimed at reviewing the history, biological efficacy, advantages, disadvantages, and concerns linked to alpha 1-PI recombinant DNA and site-specific mutagenesis technology.