In a series of experiments, they then showed that the same cellular machinery could be used to convert other large protein-coding RNAs into DISE siRNAs. And remarkably, they found that about 3 percent of all the coding RNAs in our genome could be processed to serve this purpose – thanks to the wide distribution of our kill-switch sequence.
"Now that we know the kill code, we can trigger the mechanism without having to use chemotherapy and without messing with the genome,” Peter said in a press release last month. He notes that even next-generation medications and emerging gene therapy approaches fail to treat aggressive cancers – such as pancreatic, lung, brain, and ovarian types – because they target the activity of just one gene at a time, yet the diseases are driven by multiple genes.
The DISE pathway, on the other hand, kills cancer cells in a brutal, simultaneous attack. "It's like committing suicide by stabbing yourself, shooting yourself and jumping off a building all at the same time. You cannot survive," he explained in 2017. All the research conducted thus far indicates that cancer cells cannot gain resistance to DISE.
In a proof-of-concept study published in Oncotarget last year (yet another in the recent flurry of papers), the prolific Northwestern team used nanoparticles to deliver DISE siRNAs to the cells of human ovarian tumors that had been implanted in mice. The treatment resulted in a profound reduction in tumor growth without harmful side effects. Work to boost the efficiency of the therapy is already underway.
"Based on what we have learned in these [past several] studies, we can now design artificial microRNAs that are much more powerful in killing cancer cells than even the ones developed by nature," Peter concluded.