ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
WNT-modulating gene silencers as a gene therapy for osteoporosis, bone fracture, and critical-sized bone defects.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 59 citations in OpenAlex.
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- Bone-seeking nanomaterials for rebalancing bone remodeling in osteoporosis.International journal of pharmaceutics: X · 2026Review
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- Updated Advances on Drugs and Bone-Targeting Nanoparticles for Osteoporosis Therapy: Carrier Materials, Modification, Function Mechanism, and Applications-A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts.Scientific reports · 2025Article
- Modern Strategies for Osteoporosis Therapy: Current Status and Prospects for Targeted Intervention.International journal of molecular sciences · 2025Review
- Depletion of mmu-miR-185 enhances osteocyte connectivity and suppresses bone fragility through the interaction between ARL8B and RAB5A.Stem cell research & therapy · 2025Article
- Methyltransferase-like 14 mediated FOXP1 m6A modification alleviates osteoporosis by regulating the Wnt/β-catenin pathway.Journal of molecular histology · 2025Article
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Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Treating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/β-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.