Minisymposium 28: Biotechnology

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Abs # M2801: Towards "humanization" of the plant N-glycan maturation pathway

Presenter:	faye, loic       Contact Presenter
Authors	faye, loic  (A)   Gomord, veronique  (A)
Affiliations:	(A): cnrs umr 6037

As illustrated with the production of several antibodies in different plant expression systems plants have the capacity to synthesize highly complex heterologous proteins. Particularly plants are able to perform most post-translational maturations required for a human protein to be biologically active. For instance, plants glycosylate mammalian glycoproteins. However, they are unable to reproduce "a l'identique" a human type glycosylation, as also observed with any other heterologous expression sysem. As a result, structural differences observed between plant and mammalian N-glycans are responsible for the immunogenicity of recombinant glycoproteins produced in plant expression systems (Gomord et al 2005). Today, the potential immunogenicity of glycosylated plant-made pharmaceuticals in humans is one of the main hurdles for molecular pharming related to the production of therapeutic proteins for parenteral administration. Therefore, inhibiting plant-specific post-translational modifications to obtain "humanized", non-immunogenic N-glycans on plant-made pharmaceuticals is a pre-requisite to fully benefit from the potential that plants offer for the production of biopharmaceuticals.This presentation will focus on the strategies we have recently developed to humanize N-glycosylation in alfalfa by reducing the immunogenicity of plant N-glycans. Such strategies include a knock-out of plant specific N-glycan maturation enzymes such as β1,2xylosyltransferase and α1,3 fucosyltransferases or a knock-in and targeted expression of human β1,4 galactosyltransferase. Our progress towards a complete humanization of plant N-glycans by reconstruction of the human N-glycan sialylation pathway in planta will also be presented.