The Indiana Center for Regenerative Medicine and Engineering (ICRME) of Indiana University School of Medicine hosts tissue nanotransfection regenerative medicine (TNT) technology that achieves reprogramming of functional tissues in the living body. Last year, ICRME researchers published on how to manufacture TNT 2.0 silicon chip hardware in Nature Protocol. Now, his research demonstrates for the first time that TNT can serve as a non-viral, topical gene delivery delivery device.
TNT is a minimally invasive device that can reprogram tissue function in the living body by applying harmless electrical spark pulses to deliver specific genes of interest to the skin.
TNT-based delivery can achieve cell-specific gene editing. Your skin has thousands of genes and in chronic wounds many key genes are silenced by DNA methylation. TNT-based gene editing technology can remove this barrier. “
Chandan K. Sen, PhD, corresponding author, J. Stanley Battersby Chair and Distinguished Professor of Surgery, Director of ICRME at the UI School of Medicine and Executive Director of the Center for Comprehensive Health Wound Care Indiana University
In this study, genome-wide methylation was observed in patients ’chronic wound tissue. This was reproduced in an experimental murine model. Editing specific TNT-based cell genes rescued wound healing. The results were recently published in the Journal of Clinical Investigation.
Previous TNT application studies reported rescue of injured legs, diabetic neuropathy, crushed nerve, and brain affected by stroke. This is the first time that gene-promoting methylation has been recognized as a critical barrier to wound healing. In this study, ICRME researchers found that P53 methylation and gene silencing as a critical barrier for skin wound epithelial-mesenchymal transition (EMT), a necessary mechanism for closing skin wounds. TNT-based non-viral keratinocyte-specific demethylation of the P53 gene rescued EMT and achieved wound closure.
Chronic wounds can cause serious and sometimes life-threatening complications due to the abundance of dying, necrotic tissue, such as cellulite, lower limb amputation, and sepsis. It is estimated that treating chronic wounds will cost the U.S. health care system $ 28 billion annually, increasing the need to try new treatments to prevent amputation, save lives, and reduce health care costs.
“Inspired by observations in patients with chronic wounds, this work has achieved an important milestone that highlights the need to silence genes at the wound site,” said lead author Kanhaiya Singh, PhD, associate professor of surgery and researcher at the ICRME.
This study was supported by the National Institute of Diabetes and Digestive and Renal Diseases, the U.S. Department of Defense, and Lilly Endowment’s INCITE program.
Source:
Indiana University School of Medicine
Magazine reference:
Singh, K., et al. (2022) Hypermethylation of DNA throughout the genome precludes healing in patients with chronic wounds by impairing the epithelial-mesenchymal transition. Journal of Clinical Research. doi.org/10.1172/JCI157279.