A team of researchers at the University of Wisconsin-Madison has developed a stimulating method to improve the delivery of costly medical treatments, specifically gene therapies. By exposing liver cells to short electric pulses, they were able to increase the intake of gene therapy material by over 40 times compared to cells that were not exposed to the pulses. This method could potentially reduce the dosage required for these treatments, making them safer and more affordable. The research was published in the journal PLOS ONE on April 30.
Gene therapy is a promising medical technology that involves replacing, altering, or introducing new genetic material into a patient’s cells to cure or compensate for genetic diseases such as cystic fibrosis, sickle-cell disease, hemophilia, and diabetes. However, one of the challenges in gene therapy is getting the right dose of genetic material into the target cells. The research at UW-Madison suggests that applying a moderate electric field to cells could help create more effective therapies without causing lasting damage to the cells.
The project began nearly a decade ago with transplant surgeon Hans Sollinger, who developed a gene therapy treatment for Type 1 diabetes by delivering the genetic code for insulin production into liver cells. Sollinger believed that the future of the treatment depended on improving delivery methods. He collaborated with Susan Hagness and John Booske, both professors of electrical and computer engineering at UW-Madison, to explore the use of electric pulses to enhance the delivery process and reduce the required dosage for treatment.
PhD student Yizhou Yao conducted experiments using human liver cells to determine whether exposing the cells to electric fields would increase the penetration of virus particles containing a fluorescent green protein used in gene therapy. The results showed that cells exposed to electrical pulses accumulated significantly more of the fluorescent protein compared to cells that did not receive the pulses. While the researchers have yet to determine the exact mechanism of action at the molecular level, they believe that the electric pulses may be opening nanopores in the cell membrane to facilitate the entry of virus particles.
Despite the passing of Hans Sollinger in May 2023, the research team is continuing to work on this project and has secured external funding to pursue the next steps. They are optimistic that the technique developed in this study will eventually progress to clinical trials. Yizhou Yao, who will graduate in 2024, acknowledges the steep learning curve of participating in a transdisciplinary study but expresses enthusiasm for contributing to a project with the ultimate goal of improving healthcare outcomes. The team is also collaborating with researchers from other institutions, such as Robert W. Holdcraft from the Cincinnati Children’s Hospital Medical Center.
