ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing rescues perfusion and diabetic ischemic wound healing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Reimagining VEGF Therapy: The Role of PLCγ2 in Pan-Organ Endothelial Networks.Advances in wound care · 2026Article
- Modulating Calcium Homeostasis via a Biomimetic Scaffold to Rescue Diabetic Ischemic Wounds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic dysregulation in osteonecrosis of the femoral head: a critical review of DNA methylation, histone modifications, and clinical translation.Journal of orthopaedic surgery and research · 2026Review
- Diabetic Wound Vasculopathy and Neuropathy: Spotlight on Wound Lipid Signaling.Advances in wound care · 2026Review
- Microneedle Strategies for Diabetic Wound Management: A Comprehensive Review of Materials, Mechanisms, and Therapeutic Outcomes.Materials today. Advances · 2026Article
- Identification of Skin Multicellular Reprogramming Factors as Potential Treatment for Nonhealing Diabetic Foot Ulcers.Advances in wound care · 2026Article
- Single-cell mapping of diabetic foot ulcers: mechanistic axes and therapeutic targets.Frontiers in medicine · 2026Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Enhancing VEGF therapy in T2D wounds with PLCγ2 epigenetic targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Tissue nanotransfection and cellular reprogramming in regenerative medicine and antimicrobial dynamics.Frontiers in bioengineering and biotechnology · 2025Review
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Authors and funding
20 authors.
Funding
Abstract
Diabetic wounds are complicated by underlying peripheral vasculopathy. Reliance on vascular endothelial growth factor (VEGF) therapy to improve perfusion makes logical sense, yet clinical study outcomes on rescuing diabetic wound vascularization have yielded disappointing results. Our previous work has identified that low endothelial phospholipase Cγ2 (PLCγ2) expression hinders the therapeutic effect of VEGF on the diabetic ischemic limb. In this work, guided by single-cell RNA sequencing of human wound edge, we test the efficacy of gene-targeted therapeutic demethylation intending to improve VEGF-mediated neovascularization. PLCγ2 expression was diminished in all five identified diabetic wound-edge endothelial subclusters encompassing arterial, venous, and capillary cells. Such low expression was associated with hypermethylated PLCγ2 promoter. PLCγ2 promoter was also hypermethylated at murine diabetic ischemic wound edge. To specifically demethylate endothelial PLCγ2 promoter during VEGF therapy, a CRISPR-dCas9-based demethylation cocktail was delivered to the ischemic wound edge using tissue nanotransfection (TNT) technology. Demethylation-based upregulation of PLCγ2 during VEGF therapy improved wound tissue blood flow with an increased abundance of von Willebrand factor (vWF)
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Registered trials
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