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Currently, the only U.S. food and drug administration\u2010approved treatment for A1AT disorders is intravenous augmentation therapy with human plasma\u2010derived A1AT (pdA1AT). In addition to its limited supply, this approach poses a risk of infection transmission, since it uses therapeutic A1AT harvested from donors. To address these issues, we sought to generate recombinant human A1AT (rhA1AT) that is comparable to its plasma\u2010derived counterpart using glycoengineered Chinese Hamster Ovary (geCHO\u2010L) cells. By perturbing nine key genes that are part of the CHO glycosylation machinery and expressing the human ST6GAL1 and A1AT genes, we obtained stable, high producing geCHO\u2010L lines that produced rhA1AT having a highly similar glycoprofile to pdA1AT. Additionally, the rhA1AT demonstrated in vitro activity and in vivo half\u2010life comparable to commercial pdA1AT. Thus, we anticipate that this platform will help produce human\u2010like recombinant plasma proteins, thereby providing a more sustainable and reliable source of therapeutics that are cost\u2010effective and better\u2010controlled regarding purity, clinical safety, and quality.<\/jats:p>","DOI":"10.1002\/bit.70285","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:11:13Z","timestamp":1782907873000},"page":"2605-2612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycoengineered Recombinant Alpha1\u2010Antitrypsin Results in Comparable In Vitro and In Vivo Activities to Human Plasma\u2010Derived Protein"],"prefix":"10.1002","volume":"123","author":[{"given":"Frances","family":"Rocamora","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of California, San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Lin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center University of Georgia Athens Georgia USA"},{"name":"Center for Molecular Medicine, University of Georgia Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Schoffelen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, National Biologics Facility Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Arnsdorf","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, National Biologics Facility Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Toth","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research University of Maryland Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul S.","family":"Yunus","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research University of Maryland Rockville Maryland USA"},{"name":"NeuImmune, Inc. 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