Scientists in Japan have made a breakthrough in the fight against cancer using artificial DNA. Lab tests successfully targeted and destroyed human cervical and breast cancer cells, as well as mouse malignant melanoma cells.
Hairpin-shaped DNA interacts with microRNA in cancer cells, activating an immune response.
University of Tokyo researchers have made a breakthrough in the fight against cancer with the use of artificial
Cancer is a disease that affects millions of people globally. Cancer is one of the leading causes of death, with approximately 9.6 million deaths occurring in 2018. It is estimated that one in five men and one in six women will develop cancer in their lifetime.
Cancer is a sadly familiar global health concern and current methods of treatment have their limitations. However, drugs based on nucleic acids — namely DNA and
Nucleic 
Oncolytic DNA hairpin pairs (oHPs) are introduced to the cancer cell. When the oHPs encounter the tumor-causing overexpressed microRNA (miRNA), they unravel to connect with the miRNA and each other to form longer DNA strands. These elongated strands then trigger an immune response, the body’s built-in defense mechanism, which inhibits further tumor growth. Credit: 2022 Akimitsu Okamoto
Cancer cells can overexpress, or make too many copies of, certain DNA or RNA molecules, causing them to not function normally. The team created artificial oncolytic (cancer-killing) hairpin DNA pairs called oHPs. These oHPs were triggered to form longer DNA strands when they encountered a short (micro) RNA called miR-21, which is overexpressed in some cancers.
Typically, oHPs don’t form longer strands due to their curved hairpin shape. However, when the artificial oHPs enter a cell and encounter the target microRNA, they open up to combine with it and form a longer strand. This then causes the immune system to recognize the presence of the overexpressed miR-21 as dangerous and activate an innate immune response, which ultimately leads to the death of the cancer cells.
The tests were effective against overexpressed miR-21 found in human cervical cancer-derived cells, human triple-negative breast cancer-derived cells, and mouse malignant melanoma-derived cells. “The formation of long DNA strands due to the interaction between short DNA oHPs and overexpressed miR-21, found by this research group, is the first example of its use as a selective immune amplification response which can target tumor regression, providing a new class of nucleic acid drug candidates with a mechanism that is completely different from known nucleic acid drugs,” said Okamoto.
“The results of this study are good news for doctors, drug discovery researchers, and cancer patients, as we believe it will give them new options for drug development and medication policies. Next, we will aim for drug discovery based on the results of this research, and examine in detail the drug efficacy, toxicity, and potential administration methods.” This research still has many steps to go before a treatment can be made available, but the team is confident in the benefits of nucleic acids for new drug discovery.
Reference: “Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly” by Kunihiko Morihiro, Hiraki Osumi, Shunto Morita, Takara Hattori, Manami Baba, Naoki Harada, Riuko Ohashi and Akimitsu Okamoto, 20 December 2022, Journal of the American Chemical Society.
DOI: 10.1021/jacs.2c08974
The study was funded by JST ACT-X, JSPS KAKENHI, an AMED Grant, and the Hitachi Global Foundation.