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Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva

Gene Therapy volume 19, pages 781–785 (2012)Cite this article

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by progressive heterotopic bone formation. Currently, no definitive treatment exists for FOP. The activin receptor type IA / activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for FOP, and disease-associated ALK2 mutations have been found. Chemical inhibitors to the pathogenic ALK2 receptors are considered possible medical agents for FOP, but their adverse effects on normal ALK2 and other receptors cannot be excluded. Here we describe another treatment strategy for FOP using allele-specific RNA interference (ASP-RNAi), and show modified small interfering RNAs (siRNAs) conferring allele-specific silencing against disease-causing ALK2 mutants found in FOP, without affecting normal ALK2 allele. Thus, the siRNAs presented here may become novel therapeutic agents for FOP, and their induced ASP-RNAi may pave the way for the achievement of radical treatment of FOP and/or for the relief of its severe symptoms.

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Acknowledgements

This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan and from the National Hospital Organization, and also by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and by Grant-in-Aid for Young Scientists (Start-up).

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Authors and Affiliations

  1. Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan

    M Takahashi & H Hohjoh

  2. Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Hidaka-shi, Saitama, Japan

    T Katagiri

  3. Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan

    H Furuya

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  1. M Takahashi
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  2. T Katagiri
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  3. H Furuya
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  4. H Hohjoh
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Correspondence to H Hohjoh.

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Takahashi, M., Katagiri, T., Furuya, H. et al. Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva. Gene Ther 19, 781–785 (2012). https://doi.org/10.1038/gt.2011.193

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