Title: “Revolutionizing Gene Therapy: Electric Pulses Increase Cellular Uptake of Genetic Material by 40 Times”
Gene therapy is a promising field with the potential 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 delivering the right dose of genetic material into the target cells. A new study published in PLOS ONE on April 30 addresses this issue by revealing that exposing liver cells to short electric pulses increases the uptake of gene therapy material by more than 40 times compared to cells that were not exposed to pulsed electric fields. This method could significantly reduce the dosage needed for these treatments, making them safer and more affordable.
The research began nearly a decade ago when Hans Sollinger, a transplant surgeon at UW-Madison, developed a gene therapy treatment for Type 1 diabetes, an autoimmune disease that attacks the pancreas. Sollinger’s treatment delivered the genetic code for insulin production into liver cells using an adeno-associated virus. However, Sollinger believed that the future of the treatment hinged on delivery. He turned to Susan Hagness and John Booske, both UW-Madison professors of electrical and computer engineering, to help create a more efficient and localized delivery process.
The team explored the use of electric pulses to make the delivery process more efficient and reduce the dosage needed. Previous research has shown that exposing cells to electric fields can increase the ability of molecules to move through the cell membrane into the interior of a cell. In this latest study, PhD student Yizhou Yao sought to determine whether the technique would increase the penetration of virus particles into liver cells. Yao exposed batches of human hepatoma cells to various concentrations of the gene therapy virus particles containing a fluorescent green protein. She used a pair of electrodes to deliver an 80-millisecond electric pulse to some samples, then incubated all the cells for 12 hours.
The results showed that only a small percentage of the cells that had not received the electrical pulses glowed green. In contrast, those cells that had received a zap accumulated about 40 times the amount of the fluorescent green proteins delivered by the virus. While the study provided compelling evidence that the pulses helped facilitate the virus’s penetration of the cell walls, the team is still working to discover exactly how the process works at the molecular level.
Sadly, Sollinger passed away in May 2023, but his legacy will live on through the ongoing research on this project and the work of other groups. The electrical engineering researchers are pursuing next steps with external funding and are optimistic that ultimately the technique will translate into clinical trials. The potential of this new method could revolutionize gene therapy and make it more accessible and affordable for patients worldwide.
In summary, this new study published in PLOS ONE reveals that exposing liver cells to short electric pulses increases the uptake of gene therapy material by more than 40 times compared to cells that were not exposed to pulsed electric fields. This method could significantly reduce the dosage needed for these treatments, making them safer and more affordable. The research has the potential to revolutionize gene therapy and make it more accessible and affordable for patients worldwide.