University of Pittsburgh researchers have developed a novel approach to augment VEGF therapy for ischemic tissue revascularization using epigenetic principles. By targeting the epigenetic silencing of key endothelial genes, this technology enhances the efficacy of VEGF therapy, improving blood flow and wound healing in diabetic ischemic tissues. This innovative method could significantly advance treatments for diabetic wounds and other ischemic conditions.
Description
The technology addresses the challenge of poor perfusion in diabetic wounds complicated by ischemia. Researchers identified that hyperglycemia leads to DNA methylation-based silencing of the PLCγ2 gene, hindering VEGF therapy. Using a CRISPR/dCas9-based demethylation cocktail delivered via tissue nano-transfection (TNT) technology, the PLCγ2 promoter is specifically demethylated in endothelial cells during VEGF therapy. This demethylation upregulates PLCγ2, enhancing blood flow and vascularization in the wound tissue. The approach activates the p42/p44-MAPK>HIF1α pathway, resulting in improved wound closure and tissue perfusion.
Applications
• Enhancing VEGF therapy for diabetic wound healing
• Improving revascularization in ischemic tissues
• Potential applications in other ischemic conditions
Advantages
This technology offers several unique advantages. It combines epigenetic editing with VEGF therapy to enhance revascularization and wound healing. The use of CRISPR/dCas9-based demethylation is a novel approach that targets the underlying epigenetic mechanisms hindering VEGF efficacy. The technology has shown promising results in improving blood flow and wound closure in diabetic ischemic tissues, potentially reducing the need for more invasive treatments.
Invention Readiness
The concept has been defined and validated through in vivo studies using diabetic mouse models. Researchers demonstrated that demethylation of the PLCγ2 promoter during VEGF therapy significantly improved tissue perfusion and wound healing. The technology is in the developmental stage, with ongoing research aimed at optimizing the demethylation cocktail and exploring its potential in clinical trials.
IP Status
Patent pending
