"Hairpins" made of artificial DNA clasp and kill cancer
Researchers in Japan have demonstrated a promising new cancer treatment. The team developed artificial DNA sequences shaped like hairpins that latch onto molecules overexpressed in cancer and trigger a strong immune response.
Drugs based on nucleic acids – the “NA” in DNA and RNA – are emerging as a new technique to treat a range of diseases. Most famously, the mRNA-based vaccines for COVID-19 accelerated the field, and the companies behind them are now looking into vaccines against other viruses like herpes, and even diseases like cancer.
The latter was the focus of the new study from researchers at the University of Tokyo. Nucleic acid-based drugs have some trouble distinguishing between healthy cells and cancerous ones, which can lead to some dangerous immune reactions. So the team developed artificial DNA molecules that were specially designed to only target cancer cells.
The key is the shape of these molecules – in this case, they bent back over themselves to resemble hairpins, earning them the name which they called oncolytic hairpins (oHPs). The team chemically synthesized these DNA molecules in pairs, which were made to react with a micro RNA sequence called miR-21, which is overexpressed in some types of cancer cells.
When the oHPs encounter miR-21, they connect to them and then unravel themselves to form a much longer DNA strand. This then alerts the immune system to their presence, mounting a response that can clear the cancer cells out.
The team tested the technique in lab dish cultures of human cervical and breast cancer cells, as well as melanoma in live mice. In all cases, the oHPs were effective not only at killing the tumors, but preventing the growth of further cancerous tissue.
“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 Professor Akimitsu Okamoto, co-lead author of the study.
As promising as the method sounds, it’s of course still very early days, and much more work needs to be done before it could translate to an available treatment for human patients. That includes investigating efficacy and toxicity in more detail.
The research was published in the Journal of the American Chemical Society.
Source: University of Tokyo