Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
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| Authors: | He, X; Haselhorst, T; von Itzstein, M; Kolarich, D; Packer, NH; Gloster TM;Vocadlo, DJ; Clarke, LA; Qian, Y; Kermode, AR |
| Year: | 2012 |
| Journal: | Nature Communications 3: Article number: 1062 Article Link (DOI) PubMed |
| Title: | Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease |
| 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. |
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