ABSTRACT Alpha-1 antitrypsin (A1AT) is well-established as a biotherapeutic used for the treatment of alpha-1 antitrypsin deficiency, and shows promise for treating a variety of other diseases. However, A1AT augmentation therapy carries unnecessary risk since it relies upon the weekly transfusion of plasma-derived product, which presents supply chain and contaminant risks. This could be remedied with recombinant A1AT, if it adequately matches or improves upon the plasma-derived product, including its post-translational modifications and functional attributes. However, major hurdles to the development of recombinant A1AT exist, since post- translational modifications, such as glycosylation, impact drug activities and half-life, and it has remained challenging to match glycosylation of recombinant A1AT to the plasma derived isoforms. Here we developed a large panel of diverse GMP-ready glycoengineered CHO (geCHO) cell lines that allowed us to discover a host cell line, geCHO-L, that matches glycosylation of the plasma derived product. Here we will demonstrate our platform not only allows us to identify a CHO clone matches the glycosylation of the approved product, but that we can also match the function and half-life of the approved A1AT to enable the manufacturing of a recombinant A1AT to increase the safety and protect the supply of therapeutic A1AT. We further engineer the recombinant A1AT to obtain a product with improved activity and half-life as a candidate therapeutic for alpha-1 antitrypsin deficiency and other diseases.