Bioengineering: alpha 1-proteinase inhibitor site-specific mutagenesis. The prospect for improving the inhibitor.
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.
Luisetti
M
M
Istituto di Tisiologia e Malattie Apparato Respiratorio, Università di Pavia, Italy.
Travis
J
J
D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009504:Neutrophils / Q000201:enzymology; D010641:Phenotype; D011656:Pulmonary Emphysema / Q000503:physiopathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012907:Smoking / Q000503:physiopathology; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000627:therapeutic use*; D019896:alpha 1-Antitrypsin Deficiency
D011994:Recombinant Proteins; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase