Electric Pulses Enhance Liver Cell Uptake in Gene Therapy

Electric Pulses Enhance Liver Cell Uptake in Gene Therapy

May 8, 2024 : A recent study published in PLOS ONE has unveiled a promising technique for improving the efficacy of gene therapy in liver cells. The research, conducted by a collaborative team at the University of Wisconsin-Madison, explored using brief electrical pulses to augment the cellular uptake of gene therapy vectors.

Gene therapy represents a revolutionary approach to treating a wide spectrum of genetic disorders by introducing functional genetic material directly into a patient’s cells. This approach holds immense potential for diseases affecting the liver, a vital organ responsible for numerous critical metabolic functions. However, a significant challenge associated with current gene therapy methods is ensuring the efficient delivery of therapeutic vectors – the carriers that ferry the genetic material – into targeted cells.

The study investigated the potential of utilizing short electrical pulses, known as pulsed electric fields (PEFs), to enhance the permeability of the cell membrane in liver cells, thereby facilitating the entry of gene therapy vectors. In their experiments, the researchers employed human hepatoma cells, a well-established model system for studying liver function. These cells were exposed to varying concentrations of viral particles carrying a reporter gene encoding green fluorescent protein (GFP). GFP, readily detectable under a microscope, was a visual indicator of successful gene therapy vector uptake.

Concurrent with the introduction of viral particles, the researchers subjected the cells to precisely controlled PEFs. The results were remarkably encouraging. Compared to cells not receiving PEF treatment, those exposed to the electrical pulses exhibited a significant increase in GFP expression, signifying a substantially enhanced uptake of the gene therapy vectors. The findings revealed that PEFs could augment cellular uptake over 40 times, suggesting a potentially transformative impact on gene therapy efficacy.

The proposed approach offers several potential advantages. By facilitating the delivery of gene therapy vectors at lower doses, PEFs could contribute to improved safety profiles for these treatments. Lower doses inherently translate into a reduced risk of adverse side effects. Additionally, enhanced vector uptake could pave the way for developing more potent gene therapies, potentially leading to more robust therapeutic outcomes.

The study’s senior author, Professor Susan Hagness, an electrical engineer at the University of Wisconsin-Madison, emphasized the significance of these findings. “This research suggests that electric pulses could be a valuable tool for improving gene therapy delivery to the liver,” she stated. “By increasing the efficiency with which cells take up the therapeutic vectors, we may be able to develop safer and more effective treatments for a range of liver diseases.”

While the research represents a significant step forward, further investigation is necessary. The long-term effects of PEFs on cell health and the optimal parameters for their application in a clinical setting require meticulous evaluation. Nevertheless, this study offers a compelling glimpse into the potential of PEFs to revolutionize gene therapy for liver diseases.


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