Dicker, M.; Tschofen, M.; Maresch, D.; Koenig, J.; Juarez, P.; Orzáez Calatayud, DV.; Altmann, F.... (2016). Transient glyco-engineering to produce recombinant IgA1 with defined N-and O-glycans in plants. Frontiers in Plant Science. 7(18):1-12. https://doi.org/10.3389/fpls.2016.00018
Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10251/81292
Title:
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Transient glyco-engineering to produce recombinant IgA1 with defined N-and O-glycans in plants
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Author:
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Dicker, Martina
Tschofen, Marc
Maresch, Daniel
Koenig, Julia
Juarez, Paloma
Orzáez Calatayud, Diego Vicente
Altmann, Friedrich
Steinkellner, Herta
Strasser, Richard
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UPV Unit:
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Universitat Politècnica de València. Instituto Universitario Mixto de Biología Molecular y Celular de Plantas - Institut Universitari Mixt de Biologia Molecular i Cel·lular de Plantes
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Issued date:
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Abstract:
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[EN] The production of therapeutic antibodies to combat pathogens and treat diseases, such
as cancer is of great interest for the biotechnology industry. The recent development of
plant-based expression systems has ...[+]
[EN] The production of therapeutic antibodies to combat pathogens and treat diseases, such
as cancer is of great interest for the biotechnology industry. The recent development of
plant-based expression systems has demonstrated that plants are well-suited for the
production of recombinant monoclonal antibodies with defined glycosylation. Compared
to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin
A (IgA), which is the most prevalent antibody class at mucosal sites and a promising
candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity.
Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus
antigen in glyco-engineered XT/FT Nicotiana benthamiana plants. Mass spectrometric
analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans
with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2
domain in the IgA1 alpha chain. Analysis of the peptide carrying nine potential
O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of
plant-specific modifications including hydroxyproline formation and the attachment of
pentoses. By co-expression of enzymes required for initiation and elongation of human
O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on
plant-produced IgA1. Our data demonstrate that XT/FT N. benthamiana plants can
be engineered toward the production of recombinant IgA1 with defined human-type Nand
O-linked glycans.
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Subjects:
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Monomeric IgA
,
Antibody
,
Protein glycosylation
,
N-glycosylation
,
O-glycosylation
,
Glyco-engineering
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Recombinant glycoprotein
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Plant-made pharmaceuticals
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Copyrigths:
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Reconocimiento (by)
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Source:
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Frontiers in Plant Science. (issn:
1664-462X
)
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DOI:
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10.3389/fpls.2016.00018
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Publisher:
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Frontiers Media
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Publisher version:
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http://dx.doi.org/10.3389/fpls.2016.00018
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Project ID:
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info:eu-repo/grantAgreement/FWF//TRP 242-B20/
info:eu-repo/grantAgreement/FFG//822757/
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Thanks:
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This work was supported by a grant from the Austrian Federal Ministry of Transport, Innovation and Technology (bmvit) and Austrian Science Fund (FWF): TRP 242-B20 and by the Austrian Research Promotion Agency (Laura Bassi ...[+]
This work was supported by a grant from the Austrian Federal Ministry of Transport, Innovation and Technology (bmvit) and Austrian Science Fund (FWF): TRP 242-B20 and by the Austrian Research Promotion Agency (Laura Bassi Center of Expertise "Plant produced Bio-Pharmaceuticals" Grant Nr. 822757).
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Type:
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Artículo
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