BIOENGINEERING - ALPHA(1)-PROTEINASE INHIBITOR SITE-SPECIFIC MUTAGENESIS - THE PROSPECT FOR IMPROVING THE INHIBITOR

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