4.7 Article

Production of Human Acid-Alpha Glucosidase With a Paucimannose Structure by Glycoengineered Arabidopsis Cell Culture

Journal

FRONTIERS IN PLANT SCIENCE
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fpls.2021.703020

Keywords

acid-alpha glucosidase; a1,3 mannosyltransferase; alg3; GAA; paucimannose; Pompe disease

Categories

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology (MEXT)

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This study demonstrated the production of an alternative acid-alpha glucosidase (GAA) for enzyme replacement therapy of Pompe disease in a glycoengineered Arabidopsis alg3 cell culture. Supplementing the culture medium with NaCl to a final concentration of 50 mM increased GAA production by 3.8-fold, without affecting N-glycosylation.
Plant cell cultures have emerged as a promising platform for the production of biopharmaceutics due to their cost-effectiveness, safety, ability to control the cultivation, and secrete products into culture medium. However, the use of this platform is hindered by the generation of plant-specific N-glycans, the inability to produce essential N-glycans for cellular delivery of biopharmaceutics, and low productivity. In this study, an alternative acid-alpha glucosidase (GAA) for enzyme replacement therapy of Pompe disease was produced in a glycoengineered Arabidopsis alg3 cell culture. The N-glycan composition of the GAA consisted of a predominantly paucimannosidic structure, Man(3)GlcNAc(2) (M3), without the plant-specific N-glycans. Supplementing the culture medium with NaCl to a final concentration of 50 mM successfully increased GAA production by 3.8-fold. GAA from an NaCl-supplemented culture showed a similar N-glycan profile, indicating that the NaCl supplementation did not affect N-glycosylation. The results of this study highlight the feasibility of using a glycoengineered plant cell culture to produce recombinant proteins for which M3 or mannose receptor-mediated delivery is desired.

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