Artificial DNA kills cancer cells

Japanese researchers have used artificial DNA to target and kill cancer cells in a completely new way. Described in the Journal of the American Chemical Society, the method was effective in lab tests against human cervical cancer- and breast cancer-derived cells, as well as malignant melanoma cells from mice.

Cancer is a global health concern and current methods of treatment have their limitations. However, drugs based on nucleic acids — namely DNA and RNA, the vital information-carrying molecules — can control the biological functions of cells, and are expected to transform the future of medicine and provide a significant boost towards efforts to overcome cancer and other hard-to-treat illnesses, caused by viruses and genetic diseases.

A research group at The University of Tokyo, led by Assistant Professor Kunihiko Morihiro and Professor Akimitsu Okamoto, were inspired to create a new anticancer drug using artificial DNA. Okamoto explained, “We thought that if we can create new drugs that work by a different mechanism of action from that of conventional drugs, they may be effective against cancers that have been untreatable up to now.”

Nucleic acid drug use for cancer treatment has been challenging because it is difficult to make the nucleic acids distinguish between cancer cells and other healthy cells. This means there is a risk of adversely affecting the patient’s immune system if healthy cells are inadvertently attacked. The team was however able to develop a chemically synthesised, hairpin-shaped DNA strand that can activate a natural immune response to target and kill specific cancerous cells.

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 microRNA 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 recognise 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 and prevents further growth of cancerous tissue.

The DNA proved 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. Okamoto said, “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 tumour regression, providing a new class of nucleic acid drug candidates with a mechanism that is completely different from known nucleic acid drugs.”

The 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. “Next,” Okamoto said, “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.”

Image caption: The hairpin shape of oHPs is usually fixed, just like with metal bobby pins, so these new artificial oHPs are unique in the way they can unravel. Image credit: iStock.com/AlesVeluscek