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Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva.
Gene Ther. 2012 Jul; 19(7):781-5.GT

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.

Authors+Show Affiliations

Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22130450

Citation

Takahashi, M, et al. "Disease-causing Allele-specific Silencing Against the ALK2 Mutants, R206H and G356D, in Fibrodysplasia Ossificans Progressiva." Gene Therapy, vol. 19, no. 7, 2012, pp. 781-5.
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. 2012;19(7):781-5.
Takahashi, M., Katagiri, T., Furuya, H., & Hohjoh, H. (2012). Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva. Gene Therapy, 19(7), 781-5. https://doi.org/10.1038/gt.2011.193
Takahashi M, et al. Disease-causing Allele-specific Silencing Against the ALK2 Mutants, R206H and G356D, in Fibrodysplasia Ossificans Progressiva. Gene Ther. 2012;19(7):781-5. PubMed PMID: 22130450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva. AU - Takahashi,M, AU - Katagiri,T, AU - Furuya,H, AU - Hohjoh,H, Y1 - 2011/12/01/ PY - 2011/12/2/entrez PY - 2011/12/2/pubmed PY - 2012/9/14/medline SP - 781 EP - 5 JF - Gene therapy JO - Gene Ther VL - 19 IS - 7 N2 - 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. SN - 1476-5462 UR - https://www.unboundmedicine.com/medline/citation/22130450/Disease_causing_allele_specific_silencing_against_the_ALK2_mutants_R206H_and_G356D_in_fibrodysplasia_ossificans_progressiva_ L2 - https://doi.org/10.1038/gt.2011.193 DB - PRIME DP - Unbound Medicine ER -