Scientists at the University of Tokyo, Japan have designed an artificial hairpin-like DNA molecule which is able to target and kill cancer cells by binding to microRNA (miRNA) molecules that are overproduced in certain cancers.
Artificial nucleic acids such as DNA, and RNA have recently been receiving a lot of attention as potential cancer treatments. Advantages of these artificial molecules include recognition by a variety of cellular receptors and the ability to stimulate innate immune responses. Unfortunately, some molecules tend to have a low selectivity for cancer cells leading to a risk for systemic immunotoxicity.
Reporting in the Journal of the American Chemical Society, a team of researchers at the University of Tokyo is aiming to overcome this issue by developing a hairpin DNA assembly technology called oHP enabling cancer selective immune activation. The method was effective in laboratory tests against human cervical cancer and breast-cancer derived cells as well as malignant melanoma cells in mice.
“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,” said Akimitsu Okamoto, PhD, professor at the University of Tokyo and senior author of the study.
The hairpin DNA´s mechanism of action is based on cancer cells´ ability to overexpress certain DNA or RNA molecules leading to abnormal functions. The oHPs created by the scientists react to overexpression of a specific miRNA (miR-12) by forming longer DNA strands and binding to the miR-12 molecule. These combined structures are recognized by the innate immune system, causing an immune response and targeted elimination of the cancer 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.”
“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 method,” Okamoto concluded in a press statement.