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Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody

Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb...

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Autores principales: Lee, Jeong-Hwan, Park, Da-Young, Lee, Kyung-Jin, Kim, Young-Kwan, So, Yang-Kang, Ryu, Jae-Sung, Oh, Seung-Han, Han, Yeon-Soo, Ko, Kinarm, Choo, Young-Kug, Park, Sung-Joo, Brodzik, Robert, Lee, Kyoung-Ki, Oh, Doo-Byoung, Hwang, Kyung-A, Koprowski, Hilary, Lee, Yong Seong, Ko, Kisung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744537/
https://www.ncbi.nlm.nih.gov/pubmed/23967055
http://dx.doi.org/10.1371/journal.pone.0068772
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author Lee, Jeong-Hwan
Park, Da-Young
Lee, Kyung-Jin
Kim, Young-Kwan
So, Yang-Kang
Ryu, Jae-Sung
Oh, Seung-Han
Han, Yeon-Soo
Ko, Kinarm
Choo, Young-Kug
Park, Sung-Joo
Brodzik, Robert
Lee, Kyoung-Ki
Oh, Doo-Byoung
Hwang, Kyung-A
Koprowski, Hilary
Lee, Yong Seong
Ko, Kisung
author_facet Lee, Jeong-Hwan
Park, Da-Young
Lee, Kyung-Jin
Kim, Young-Kwan
So, Yang-Kang
Ryu, Jae-Sung
Oh, Seung-Han
Han, Yeon-Soo
Ko, Kinarm
Choo, Young-Kug
Park, Sung-Joo
Brodzik, Robert
Lee, Kyoung-Ki
Oh, Doo-Byoung
Hwang, Kyung-A
Koprowski, Hilary
Lee, Yong Seong
Ko, Kisung
author_sort Lee, Jeong-Hwan
collection PubMed
description Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar levels of binding activity to the FcγRI receptor (CD64). The mAb(P)K had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAb(P) had mainly Golgi type glycans (96.8%) similar to those seen with mAb(H). Confocal analysis showed that the mAb(P)K was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAb(P) with KDEL in the ER. Both mAb(P) and mAb(P)K disappeared with similar trends to mAb(H) in BALB/c mice. In addition, mAb(P)K was as effective as mAb(H) at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAb(P) by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant.
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spelling pubmed-37445372013-08-21 Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody Lee, Jeong-Hwan Park, Da-Young Lee, Kyung-Jin Kim, Young-Kwan So, Yang-Kang Ryu, Jae-Sung Oh, Seung-Han Han, Yeon-Soo Ko, Kinarm Choo, Young-Kug Park, Sung-Joo Brodzik, Robert Lee, Kyoung-Ki Oh, Doo-Byoung Hwang, Kyung-A Koprowski, Hilary Lee, Yong Seong Ko, Kisung PLoS One Research Article Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar levels of binding activity to the FcγRI receptor (CD64). The mAb(P)K had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAb(P) had mainly Golgi type glycans (96.8%) similar to those seen with mAb(H). Confocal analysis showed that the mAb(P)K was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAb(P) with KDEL in the ER. Both mAb(P) and mAb(P)K disappeared with similar trends to mAb(H) in BALB/c mice. In addition, mAb(P)K was as effective as mAb(H) at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAb(P) by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant. Public Library of Science 2013-08-15 /pmc/articles/PMC3744537/ /pubmed/23967055 http://dx.doi.org/10.1371/journal.pone.0068772 Text en © 2013 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Jeong-Hwan
Park, Da-Young
Lee, Kyung-Jin
Kim, Young-Kwan
So, Yang-Kang
Ryu, Jae-Sung
Oh, Seung-Han
Han, Yeon-Soo
Ko, Kinarm
Choo, Young-Kug
Park, Sung-Joo
Brodzik, Robert
Lee, Kyoung-Ki
Oh, Doo-Byoung
Hwang, Kyung-A
Koprowski, Hilary
Lee, Yong Seong
Ko, Kisung
Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title_full Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title_fullStr Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title_full_unstemmed Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title_short Intracellular Reprogramming of Expression, Glycosylation, and Function of a Plant-Derived Antiviral Therapeutic Monoclonal Antibody
title_sort intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744537/
https://www.ncbi.nlm.nih.gov/pubmed/23967055
http://dx.doi.org/10.1371/journal.pone.0068772
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