Tissue nano transfection technology helps close complex skin wounds with non-viral topical gene editing.

Tissue nano transfection technology helps close complex skin wounds

The Indiana Center for Regenerative Medicine and Engineering (ICRME) is part of the Indiana University School of Medicine. It is where tissue nano transfection (TNT), a regenerative medicine technology, is used to re-program living body tissues so that they work better. In Nature Protocol, researchers from ICRME wrote about how to make the hardware for the TNT 2.0 silicon chip last year. Their research shows for the first time that TNT can be used as a way to deliver gene-editing tools that don’t use viruses.
TNT is a device that can change the way tissues work in a living body by sending specific genes of interest to the skin through pulses of harmless electric sparks.

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Chandan K. Sen, Ph.D., the J. Stanley Battersby Chair and distinguished professor of surgery, director of the ICRME at IU School of Medicine, and executive director of the Indiana University Health Comprehensive Wound Care Center, said that cell-specific gene editing can be done with TNT-based delivery. “Your skin has thousands of genes, and when you have a wound that doesn’t heal, DNA methylation turns off many important genes.” “Gene-editing technology that is based on TNT can get rid of this problem.”

In this study, it was found that patients with chronic wounds had methylation all over their genomes. This was shown to work in an experiment with mice. Cell-specific gene editing with TNT helped wounds heal. The Journal of Clinical Investigation just put out the results.

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In previous studies of how TNT can be used, people with broken legs, diabetic neuropathy, crushed nerves, and stroke-affected brains were helped. This is the first time that methylation of gene promoters has been seen as a major obstacle to healing wounds. In this study, researchers from ICRME found that P53 methylation and gene silencing are key barriers to cutaneous wound epithelial-to-mesenchymal transition (EMT), a process that is needed to heal skin wounds. EMT-based, non-viral demethylation of the P53 gene in keratinocytes only saved EMT and led to wound healing.

Due to a large amount of dead and dying tissue, chronic wounds can lead to serious and sometimes life-threatening problems, such as cellulitis, amputation of the lower extremities, and sepsis. It is estimated that treating chronic wounds costs the U.S. healthcare system $28 billion per year. This makes it even more important to try out new treatments to prevent amputation, save lives, and lower health care costs.

“This work has reached an important milestone that shows how important it is to turn on genes at the wound site,”

said Kanhaiya Singh, Ph.D., who is an assistant professor of surgery and an investigator at the ICRME. Singh is also the first author of the paper.

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