Intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody
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- Intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody
- J H Lee; D Y Park; K J Lee; Y K Kim; Y K So; J S Ryu; S H Oh; Y S Han; K Ko; Y K Choo; S J Park; R Brodzik; K K Lee; Doo-Byoung Oh; K A Hwang; H Koprowski; Y S Lee; K Ko
- Bibliographic Citation
- PLoS One, vol. 8, no. 8, pp. 68772-68772
- Publication Year
- Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAbPs), 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 mAbP 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 mAbP SO57 with KDEL (mAbPK) were significantly higher than those of mAbP SO57 without KDEL (mAbP) regardless of the transcription level. The Fc domains of both purified mAbP and mAbPK and hybridoma-derived mAb (mAbH) had similar levels of binding activity to the FcγRI receptor (CD64). The mAbPK had glycan profiles of both oligomannose (OM) type (91.7%) and Golgi type (8.3%), whereas the mAbP had mainly Golgi type glycans (96.8%) similar to those seen with mAbH. Confocal analysis showed that the mAbPK was co-localized to ER-tracker signal and cellular areas surrounding the nucleus indicating accumulation of the mAbP with KDEL in the ER. Both mAbP and mAbPK disappeared with similar trends to mAbH in BALB/c mice. In addition, mAbPK was as effective as mAbH at neutralizing the activity of the rabies virus CVS-11. These results suggest that the ER localization of the recombinant mAbP by KDEL reprograms OM glycosylation and enhances the production of the functional antivirus therapeutic antibody in the plant.
- Public Library of Science
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- Aging Convergence Research Center > 1. Journal Articles
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