Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease

Xu He, Thomas Haselhorst, Mark von Itzstein, Daniel Kolarich, Nicolle H. Packer, Tracey M. Gloster, David J. Vocadlo, Lorne A. Clarke, Yi Qian and Allison R. Kermode ()
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Xu He: Simon Fraser University
Thomas Haselhorst: Institute for Glycomics, Griffith University
Mark von Itzstein: Institute for Glycomics, Griffith University
Daniel Kolarich: Macquarie University
Nicolle H. Packer: Macquarie University
Tracey M. Gloster: Simon Fraser University
David J. Vocadlo: Simon Fraser University
Lorne A. Clarke: University of British Columbia, The Child and Family Research Institute
Yi Qian: Washington University School of Medicine
Allison R. Kermode: Simon Fraser University

Nature Communications, 2012, vol. 3, issue 1, 1-9

Abstract: Abstract Lysosomal storage diseases are a class of over 70 rare genetic diseases that are amenable to enzyme replacement therapy. Towards developing a plant-based enzyme replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis I, here we expressed α-L-iduronidase in the endosperm of maize seeds by a previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization, cellular fractionation and in situ RT–PCR demonstrate that the α-L-iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived protein bodies and to protein body–ER regions, respectively, using regulatory (5′- and 3′-UTR) and signal-peptide coding sequences from the γ-zein gene. The maize α-L-iduronidase exhibits high activity, contains high-mannose N-glycans and is amenable to in vitro phosphorylation. This mRNA-based strategy is of widespread importance as plant N-glycan maturation is controlled and the therapeutic protein is generated in a native form. For our target enzyme, the N-glycan structures are appropriate for downstream processing, a prerequisite for its potential as a therapeutic protein.

Date: 2012
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DOI: 10.1038/ncomms2070

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