Recombinant Human alpha1-Antitrypsin - Expression in Pichia pastoris and Nanoencapsulation

摘要

Human alpha1-antitrypsin (AAT) is an important member of the serine protease inhibitor superfamily and plays an important role in protease-antiprotease homeostasis in lung. The current commercial plasma derived AAT has obstacles like virus contamination and source limitation. The aim of this study is the expression of AAT in yeast Pichia pastoris using recombinant DNA technology and nano-encapsulation of recombinant AAT protein using biocompatible polymer (PLGA) for controlled protein release. Human alpha1-antitrypsin (AAT) is a midsized glycoprotein which is strongly secreted in by hepatocytes. It protects tissues against the destructive effects of proteases (1). Low concentrations of AAT in the lower respiratory tract is associated with progressive and ultimately fatal emphysema (2). Augmentation therapy with natural human AAT has become available as a treatment for AAT deficient patients, but it has some fundamental problems such as the risk of virus contaminations (3) and the need for large quantities of human serum and the amount of needed protein per patient (up to 60 mg/kg of protein weekly).