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dc.contributor.authorVamvaka, Evangelia
dc.contributor.authorTwyman, Richard M.
dc.contributor.authorMelro Murad, Andre
dc.contributor.authorMelnik, Stanislav
dc.contributor.authorYi-Hui Teh, Audrey
dc.contributor.authorArcalis, Elsa
dc.contributor.authorAltmann, Friedrich
dc.contributor.authorStöger, Eva
dc.contributor.authorRech, Elibio
dc.contributor.authorMa, Julian K-C.
dc.contributor.authorChristou, Paul
dc.contributor.authorCapell Capell, Teresa
dc.description.abstractProtein microbicides against HIV can help to prevent infection but they are required in large, repetitive doses. This makes current fermenter-based production systems prohibitively expensive. Plants are advantageous as production platforms because they offer a safe, economical and scalable alternative, and cereals such as rice are particularly attractive because they could allow pharmaceutical proteins to be produced economically and on a large scale in developing countries. Pharmaceutical proteins can also be stored as unprocessed seed, circumventing the need for a cold chain. Here, we report the development of transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was predominantly aglycosylated. Nevertheless, the heavy and light chains assembled into functional antibodies with more potent HIV-neutralizing activity than other plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type glycans. Immunolocalization experiments showed that the assembled antibody accumulated predominantly in protein storage vacuoles but also induced the formation of novel, spherical storage compartments surrounded by ribosomes indicating that they originated from the endoplasmic reticulum. The comparison of wild-type and transgenic plants at the transcriptomic and proteomic levels indicated that endogenous genes related to starch biosynthesis were down-regulated in the endosperm of the transgenic plants, whereas genes encoding prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into factors that affect the functional efficacy of neutralizing antibodies in plants and the impact of recombinant proteins on endogenous gene expression.ca_ES
dc.description.sponsorshipThe authors would like to acknowledge funding from the Ministerio de Ciencia e Innovación, Spain (BIO2012-35359), the Centre CONSOLIDER on Agrigenomics funded by MICINN, Spain, and COST Action FA0804 (Molecular farming: plants as a production platform for high value proteins).ca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofPlant Biotechnology Journal, 2016, vol. 14, núm. 1, p. 97-108ca_ES
dc.rightscc-by (c) Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd, 2015ca_ES
dc.titleRice endosperm produces an underglycosylated and potent form of the HIV-neutralizing monoclonal antibody 2G12ca_ES

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cc-by (c) Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd, 2015
Except where otherwise noted, this item's license is described as cc-by (c) Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd, 2015