Model acetylcholinesterase-Fc fusion glycoprotein biotechnology system for the manufacture of an organophosphorus toxicant bioscavenging countermeasure.

Autor: Biel TG; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Faison T; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Matthews AM; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Ortega-Rodriguez U; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Falkowski VM; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Meek E; Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences College of Veterinary Medicine, Mississippi State University Mississippi State Mississippi USA., Bush X; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA.; Department of Biomedical and Pharmaceutical Sciences College of Pharmacy, University of Rhode Island Kingston Rhode Island USA., Flores M; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Johnson S; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Wu WW; Facility for Biotechnology Resources Center for Biologics Evaluation and Research, United States Food and Drug Administration Silver Spring Maryland USA., Lehtimaki M; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Shen RF; Facility for Biotechnology Resources Center for Biologics Evaluation and Research, United States Food and Drug Administration Silver Spring Maryland USA., Agarabi C; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Rao VA; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA., Chambers JE; Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences College of Veterinary Medicine, Mississippi State University Mississippi State Mississippi USA., Ju T; Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration Silver Spring Maryland USA.
Jazyk: angličtina
Zdroj: Bioengineering & translational medicine [Bioeng Transl Med] 2024 Apr 25; Vol. 9 (5), pp. e10666. Date of Electronic Publication: 2024 Apr 25 (Print Publication: 2024).
DOI: 10.1002/btm2.10666
Abstrakt: Organophosphate (OP) toxicants remain an active threat to public health and to warfighters in the military. Current countermeasures require near immediate administration following OP exposure and are reported to have controversial efficacies. Acetylcholinesterase (AChE) fused to the human immunoglobulin 1 (IgG1) Fc domain (AChE-Fc) is a potential bioscavenger for OP toxicants, but a reproducible AChE-Fc biomanufacturing strategy remains elusive. This report is the first to establish a comprehensive laboratory-scale bioprocessing strategy that can reproducibly produce AChE-Fc and AChE(W86A)-Fc which is a mutated AChE protein with reduced enzymatic activity. Characterization studies revealed that AChE-Fc and AChE(W86A)-Fc are N -glycosylated dimeric fusion glycoproteins but only AChE-Fc had the capability to bind to paraoxon (a model OP). This AChE-Fc fusion glycoprotein bioprocessing strategy can be leveraged during industrial biomanufacturing development, while the research-grade AChE-Fc proteins can be used to determine the potential clinical relevance of the countermeasure against OP toxicants.
Competing Interests: The authors have no competing interests to declare or conflicts of interest. The funding source had no part in the study design, data collection/analysis, decision to publish, or preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the United States Food and Drug Administration and the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.
(Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje