Researchers in electrical engineering at the University of Wisconsin-Madison have created a stimulating method to enhance the delivery of expensive medical treatments. This new method could potentially make the human body more responsive to specific gene therapies. The researchers achieved this by subjecting liver cells to brief electric pulses, which surprisingly made the cells more receptive to gene therapies.is that delivering genetic material into the cells is a challenge. The new method of using pulsed electric fields has shown promising results in increasing the uptake of gene therapy material by the cells. This could potentially lower the amount of dosage required for these treatments, which would make them safer and more cost-effective. The research on this method was published in the journal PLOS ONE on April 30.
Gene therapy has the potential to cure or mitigate genetic diseases by manipulating the genetic material within the patient’s cells. Diseases such as cystic fibrosis, sickle-cell disease, hemophilia, and diabetes could potentially be treated using gene therapy. However, one of the challenges of gene therapy is delivering the genetic material into the cells, which is where the new method of using pulsed electric fields comes into play.with the delivery to the cells. However, the challenge was ensuring that enough of the genetic material reached the target cells. The University of Wisconsin-Madison’s research indicated that applying a moderate electric field to the cells could potentially solve this issue. The research showed that this method did not cause any long-term damage to the recipient cells, which suggests that it could be a safe and effective approach for improving gene therapy treatments.
The initial phase of the project was initiated nearly ten years ago by Hans Sollinger, a transplant surgeon at UW-Madison. Sollinger had created a gene therapy for Type 1 diabetes, an autoimmune condition that affects the pancreas and its ability to produce insulin.
Sollinger’s treatment involved delivering the genetic information for insulin production into liver cells using an adreno-associated virus to aid in the delivery process. However, the main challenge was ensuring that an adequate amount of the genetic material successfully reached the intended cells.The role of electrical pulses in transporting therapeutic genes across cell membranes is crucial. Once inside the cells, this DNA can settle in the liver cells and produce insulin without the risk of being attacked by the immune system in the pancreas.
Although Sollinger had proven that the therapy was effective, he knew that the success of the treatment depended on its delivery. This led him to seek the expertise of Susan Hagness and John Booske, both professors of electrical and computer engineering at UW-Madison, who had experience in using electrical pulses to treat human cells.
The focus of their discussion was on achieving local and targeted delivery, exploring the possibility of effectively introducing the therapeutic genes into the cells.Hagness stated, “We are investigating the direct delivery of treatment DNA into the liver without the need to pass it through the entire body and activate the immune system. We are also exploring the use of electric pulses to enhance the delivery process and significantly reduce the required dosage.” Previous research has shown that exposing cells to electric fields can improve the movement of molecules through the cell membrane. In this study, PhD student Yizhou Yao aimed to investigate whether this technique could enhance the penetration of virus particles into liver cells. The team used human hepatoma cells for their experiments.Using a liver model system, Yao tested batches of cells with different concentrations of gene therapy virus particles containing a fluorescent green protein. She then used electrodes to apply an 80-millisecond electric pulse to some samples and incubated all the cells for 12 hours.
Upon examination 48 hours later under a fluorescence microscope, Yao observed that only a small percentage of the cells that did not receive the electrical pulses glowed green. In contrast, the cells that did receive the electric pulse accumulated about 40 times the amount of fluorescent green proteins.
The virus was delivered by electric pulses, which the study found to aid in the virus’s entry into the cell walls. While the results showed strong evidence supporting this, Booske mentioned that the team is still uncertain about the exact process at the molecular level. “There’s enough understanding of electric pulsing to confidently say that it opens nanopores through the cell membrane,” he explained. “But then Yao achieved this incredible result, and we realized that virus particles are generally larger and more complex than bare molecular particles, and they already have their own way of entering cells. So, we are not entirely sure if it’s the
It has anything to do with directly or indirectly. Sollinger died in May 2023, but his legacy will continue through ongoing research on this project and the work of other groups. The electrical engineering researchers are moving forward with external funding and are hopeful that the technique will eventually lead to clinical trials.
Yao, who will graduate in 2024, knew the study would be interdisciplinary, but didn’t realize how extensive it would be.
“I am an electrical engineer by training and don’t have a background in biology,” Yao said.The woman said that she hadn’t used a microscope since high school, so it was a bit challenging for her at first to learn how to culture cells and carry out biology protocols, but she really enjoyed the project and its goal of making the world a better place.
