Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive heterotopic ossification. More than 95% of cases are caused by a recurrent mutation (617G>A; R206H) of ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Recent studies revealed that ACVR1R206H induces heterotopic ossification by aberrant activation in response to activin A. Because ACVR1R206H is a hyperactive receptor, a promising therapeutic strategy is to decrease the activity of ACVR1 in patients. Here, we describe a method to reduce ACVR1 expression in FOP patient cells by exon skipping in ACVR1 mRNAs using phosphorodiamidate morpholino oligomers (PMOs). This strategy can be applied to the screen to select antisense oligomers to knockdown not only ACVR1 but also genes which cause other autosomal-dominant genetic diseases.
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Acknowledgments
This work was supported by the University of Alberta Faculty of Medicine and Dentistry, International FOP Association/The Canadian FOP Network Research Grant, Gilbert K. Winter Funds, the Canadian Institutes of Health Research (CIHR), the Friends of Garrett Cumming Research Funds, HM Toupin Neurological Science Research Funds, the Muscular Dystrophy Canada, the Canada Foundation for Innovation, Alberta Enterprise and Advanced Education, Rare Disease Foundation/BC Children’s Hospital Foundation Microgrant, and the Women and Children’s Health Research Institute (WCHRI).
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Maruyama, R., Yokota, T. (2018). Morpholino-Mediated Exon Skipping Targeting Human ACVR1/ALK2 for Fibrodysplasia Ossificans Progressiva. In: Yokota, T., Maruyama, R. (eds) Exon Skipping and Inclusion Therapies. Methods in Molecular Biology, vol 1828. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8651-4_32
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DOI: https://doi.org/10.1007/978-1-4939-8651-4_32
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