ArticleGlycobiology2012
Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants.
Article in Glycobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Plant molecular farming: a promising frontier for orphan drug production.Biotechnology letters · 2025Review
- The tobacco GNTI stem region harbors a strong motif for homomeric protein complex formation.Frontiers in plant science · 2023Article
- Cell Biology Methods to Study Recombinant Proteins in Seeds.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Therapeutic Approaches in Lysosomal Storage Diseases.Biomolecules · 2021Review
- Inactivation ofFrontiers in plant science · 2021Article
- Plant Platforms for Efficient Heterologous Protein Production.Biotechnology and bioprocess engineering : BBE · 2021Review
- Transient Production of Human β-Glucocerebrosidase With Mannosidic-TypeFrontiers in plant science · 2021Article
- A baculoviral system for the production of human β-glucocerebrosidase enables atomic resolution analysis.Acta crystallographica. Section D, Structural biology · 2020Article
- Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics.Frontiers in plant science · 2020Review
- Local supplementation with plant-derived recombinant human FGF2 protein enhances bone formation in critical-sized calvarial defects.Journal of bone and mineral metabolism · 2019Article
- The Production of Human β-Glucocerebrosidase inInternational journal of molecular sciences · 2018Article
- N-glycan structures and downstream mannose-phosphorylation of plant recombinant human alpha-L-iduronidase: toward development of enzyme replacement therapy for mucopolysaccharidosis I.Plant molecular biology · 2017Article
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Reduced paucimannosidic N-glycan formation by suppression of a specific β-hexosaminidase from Nicotiana benthamiana.Plant biotechnology journal · 2017Article
- The production of human glucocerebrosidase in glyco-engineered Nicotiana benthamiana plants.Plant biotechnology journal · 2016Article
- Biochemical Characterization of Human Anti-Hepatitis B Monoclonal Antibody Produced in the Microalgae Phaeodactylum tricornutum.PloS one · 2015Article
- Membrane anchors effectively traffic recombinant human glucocerebrosidase to the protein storage vacuole of Arabidopsis seeds but do not adequately control N-glycan maturation.Plant cell reports · 2014Article
- Protein N-glycosylation in eukaryotic microalgae and its impact on the production of nuclear expressed biopharmaceuticals.Frontiers in plant science · 2014Review
- Trafficking of endoplasmic reticulum-retained recombinant proteins is unpredictable in Arabidopsis thaliana.Frontiers in plant science · 2014Review
- Characterization and downstream mannose phosphorylation of human recombinant α-L-iduronidase produced in Arabidopsis complex glycan-deficient (cgl) seeds.Plant biotechnology journal · 2013Article
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Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
Abstract
There is a clear need for efficient methods to produce protein therapeutics requiring mannose-termination for therapeutic efficacy. Here we report on a unique system for production of active human lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45) using seeds of the Arabidopsis thaliana complex-glycan-deficient (cgl) mutant, which are deficient in the activity of N-acetylglucosaminyl transferase I (EC 2.4.1.101). Gaucher disease is a prevalent lysosomal storage disease in which affected individuals inherit mutations in the gene (GBA1) encoding GCase. A gene cassette optimized for seed expression was used to generate the human enzyme in seeds of the cgl (C5) mutant, and the recombinant GCase was mainly accumulated in the apoplast. Importantly, the enzymatic properties including kinetic parameters, half-maximal inhibitory concentration of isofagomine and thermal stability of the cgl-derived GCase were comparable with those of imiglucerase, a commercially available recombinant human GCase used for enzyme replacement therapy in Gaucher patients. N-glycan structural analyses of recombinant cgl-GCase showed that the majority of the N-glycans (97%) were mannose terminated. Additional purification was required to remove ∼15% of the plant-derived recombinant GCase that possessed potentially immunogenic (xylose- and/or fucose-containing) N-glycans. Uptake of cgl-derived GCase by mouse macrophages was similar to that of imiglucerase. The cgl seed system requires no addition of foreign (non-native) amino acids to the mature recombinant GCase protein, and the dry transgenic seeds represent a stable repository of the therapeutic protein. Other strategies that may completely prevent plant-like complex N-glycans are discussed, including the use of a null cgl mutant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.