A groundbreaking new approach in cancer treatment has emerged, utilizing light to disable the mitochondria, the energy-producing organelles inside cancer cells. Researchers at Ohio State University have developed a targeted gene therapy using viral vectors, specifically engineered adeno-associated viruses (AAVs), that deliver genes designed to disrupt mitochondrial function directly to cancer cells. This therapy uses light to activate these genes, leading to the collapse of the mitochondria and shutting down the cell's energy production. To further enhance the precision of this treatment, nanoparticles were employed as the delivery system. These nanoparticles ensure that the gene therapy is targeted directly to cancer cells, minimizing any potential harm to surrounding healthy tissue. The treatment has shown promising results in shrinking tumors from glioblastoma (a brain cancer) and aggressive breast cancer in mice.
The key to this innovative treatment is the mitochondria, which produce energy for cells to function. The research team, led by Professors Lufang Zhou and X. Margaret Liu, has found a way to disrupt the mitochondrial membrane using light-activated electrical currents. This breakthrough technique, named mLumiOpto, causes cancer cells to die by shutting down their energy production and triggering DNA damage.
The researchers engineered AAVs to deliver therapeutic genes directly into cancer cells. These AAVs carry genes for two crucial components: a light-sensitive protein that creates electrical currents and a bioluminescent enzyme that activates the protein. Once inside the cancer cells, the AAVs produce these proteins, and a special chemical is injected to trigger light, which activates the protein to collapse the mitochondria, ultimately leading to the death of the cancer cells. The nanoparticles used in this study further refine the delivery mechanism, enhancing the ability of the AAVs to reach the targeted cells more efficiently and ensuring greater specificity in the treatment.
A key challenge in this treatment was ensuring that the therapy targeted only cancer cells without affecting healthy tissue. To achieve this, the team incorporated a monoclonal antibody into the AAVs, which helps them specifically find and deliver the therapeutic genes to cancer cells. Nanoparticles also play a role in stabilizing and protecting the AAVs, helping to shield the therapeutic genes during their journey through the body. Experiments in mice showed that this method not only reduced tumor size but also extended the survival of mice with glioblastoma.
This research opens up exciting possibilities for treating hard-to-treat cancers such as glioblastoma and triple-negative breast cancer. The therapy has shown minimal effects on normal tissue, and further studies are underway to explore its potential in other cancers. With a provisional patent filed, this novel treatment could revolutionize cancer therapy by using the power of light, targeted AAV-based gene therapy, and nanoparticles for more effective and precise treatment.
The research team, led by Professors Lufang Zhou and X. Margaret Liu, has found a way to disrupt the mitochondrial membrane using light-activated electrical currents. This breakthrough technique, named mLumiOpto, causes cancer cells to die by shutting down their energy production and triggering DNA damage.
Created: Feb 8th, 2025
Citations:
Caldwell, E. (2024, December 17). Light-induced gene therapy disables cancer cells’ energy center. The Ohio State University. https://news.osu.edu/light-induced-gene-therapy-disables-cancer-cells-energy-center/
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