Scientists at Ohio State University are working on an innovative approach to cancer treatment by targeting the mitochondria—the energy-producing organelles in cells—to induce cancer cell death using light-induced gene therapy. They call this innovation mitochondrial luminoptogenetics or mLumiOpto. A paper detailing the process, mechanism, and initial results was published in 2024 in the journal Cancer Research. This study was supported by the U.S. Department of Defense and the National Institutes of Health.
Illuminating Cancer Treatment: mLumiOpto is an Experimental Gene Therapy that Uses Light to Target the Mitochondria of Cancer Cells
A team of researchers headed by Kai Chen and Patrick Ernst developed mLumiOpto which uses light to disrupt the mitochondria in cancer cells. Hence, by damaging this energy-producing part, the cells lose their ability to produce energy and function properly, thus causing DNA damage and triggering apoptosis or programmed cell death.
Specifics
• Gene Therapy Delivery: The entire concept behind mLumiOpto is anchored on the principles of gene therapy. Genetic information encoding a light-sensitive protein or CoChR and a bioluminescent enzyme is specifically packaged in an engineered adeno-associated virus or AAV. This virus targets only cancer cells.
• Enzyme Activation: A chemical injection activates the bioluminescent enzyme after the gene therapy is delivered. The enzyme produces light within the cell and triggers the CoChR protein to generate electrical currents. These currents disrupt the mitochondrial membrane and cause it to collapse.
• Cancer Cell Targeting: The AAV delivery system is engineered to selectively target cancer cells and spare normal cells. This is achieved by adding a cancer-specific promoter protein to drive the expression of the therapeutic genes only in cancer cells and a monoclonal antibody that targets receptors unique to cancer cells.
Results
The therapy was effective in shrinking a deadly brain tumor called glioblastoma and an aggressive form of breast cancer called triple-negative breast cancer in mice. Tumor burden significantly decreased. Survival improved in treated animals compared to untreated ones. Imagining confirmed that the effects of mLumiOpto were limited to cancer cells. Normal cells were unharmed.
Implications
Mitochondrial luminoptogenetics or mLumiOpto therapy directly disrupts the organelle itself to produce broader anti-cancer effects that lead to targeted cell death. Conventional therapies only target specific pathways in mitochondria. The use of an internal light source, rather than an external laser, also makes the technique more adaptable for clinical use.
The monoclonal antibody not only enhances targeting precision but also triggers an immune response against cancer cells. The components of the therapy are stable and compatible. Note that the researchers derive the viral vector and nanocarrier from human cells.
Researchers are planning to explore the full potential of mLumiOpto in treating glioblastoma, triple-negative breast cancer, and other cancers. They are also set to further investigate further specific immune-stimulating effects. A provisional patent has been filed. There are ongoing studies that aim to refine the technology for clinical applications.
FURTHER READING AND REFERENCE
- Chen, K., Ernst, P., Sarkar, A., Kim, S., Si, Y., Varadkar, T., Ringel, M. D., Liu, X. “Margaret,” and Zhou, L. 2024. “mLumiOpto Is a Mitochondrial-Targeted Gene Therapy for Treating Cancer.” Cancer Research. 84(23): 4049-4065. American Association for Cancer Research. DOI: 1158/0008-5472.can-24-0984