ArticleNature communications2022
Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Pharmacokinetics of Zilurgisertib With and Without Food from Single and Multiple Ascending Dose Phase 1 Studies in Healthy Adults.European journal of drug metabolism and pharmacokinetics · 2025Trial
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- USP24-dependent STAT2 stabilization mediates physiologic and pathologic bone formation.Cell death & disease · 2026Article
- Interdisciplinary Study of the Clinical Phenotype of Patients with Fibrodysplasia Ossificans Progressiva (FOP) in Dental Practice: A Cross-Sectional Clinical-Statistical Analysis.Journal of clinical medicine · 2026Article
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Gut microbiome-dependent IL-1 signaling is a mediator of ACVR1bioRxiv : the preprint server for biology · 2026Article
- Compound KTI-2338 Inhibits ACVR1 Receptor Signaling in Fibrodysplasia Ossificans Progressiva.Pharmaceutics · 2025Article
- Nature-inspired IL-1 targeted therapy to treat chronic inflammatory diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Snhg18 regulates Yap subcellular localization to maintain bone homeostasis.Nature communications · 2025Article
- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- The role of miRNAs as biomarkers in heterotopic ossification.EFORT open reviews · 2024Review
- Molecular Developmental Biology of Fibrodysplasia Ossificans Progressiva: Measuring the Giant by Its Toe.Biomolecules · 2024Review
- Animal models of tendon calcification: Past, present, and future.Animal models and experimental medicine · 2024Review
- Development of AAV-Mediated Gene Therapy Approaches to Treat Skeletal Diseases.Human gene therapy · 2024Review
- Advances in Bone-Targeting Drug Delivery: Emerging Strategies Using Adeno-Associated Virus.Human gene therapy · 2024Review
- Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva.Life science alliance · 2024Article
- Immunologic Aspects in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Heterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no prevention or treatment. Most patients with this disease harbor a heterozygous activating mutation (c.617 G > A;p.R206H) in ACVR1. Here, we identify recombinant AAV9 as the most effective serotype for transduction of the major cells-of-origin of heterotopic ossification. We use AAV9 delivery for gene replacement by expression of codon-optimized human ACVR1, ACVR1R206H allele-specific silencing by AAV-compatible artificial miRNA and a combination of gene replacement and silencing. In mouse skeletal cells harboring a conditional knock-in allele of human mutant ACVR1 and in patient-derived induced pluripotent stem cells, AAV gene therapy ablated aberrant Activin A signaling and chondrogenic and osteogenic differentiation. In Acvr1(R206H) knock-in mice treated locally in early adulthood or systemically at birth, trauma-induced endochondral bone formation was markedly reduced, while inflammation and fibroproliferative responses remained largely intact in the injured muscle. Remarkably, spontaneous heterotopic ossification also substantially decreased in in Acvr1(R206H) knock-in mice treated systemically at birth or in early adulthood. Collectively, we develop promising gene therapeutics that can prevent disabling heterotopic ossification in mice, supporting clinical translation to patients with fibrodysplasia ossificans progressiva.
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