WATERLOO – When that nasty cold hits and you’re stuck in bed sneezing with a runny nose, wouldn’t it be nice to have an inhaler that could kill the virus?
Or what about more serious viruses like SARS-CoV-2, or even cancers like glioblastoma?
A new discovery by Wilfrid Laurier University virologist and immunologist Stephanie DeWitte-Orr has the potential to change the way we target and kill cancer and virus genes in the human body.
“Sometimes cells make proteins they’re not supposed to, or they make too much protein, and it makes you sick,” said DeWitte-Orr, who was recently named a 2022 Laurier University Research Professor- 23. “What we found is a way to specifically shut down these proteins.”
The research, recently presented in a paper published in the journal “Frontiers in Immunology,” focuses on long double-stranded ribonucleic acid, or dsRNA, a nucleic acid produced by viruses. In the body, a healthy cell will use dsRNA as a “red flag” to detect when it has been infected by a virus and initiate an immune response.
In plants and invertebrates, researchers have previously been able to use dsRNA to target and stop the spread of disease in healthy and cancerous cells.
However, it was never possible in humans until now.
The process, known as RNA interference, allows DeWitte-Orr to put a variety of different sequences into the same molecule, which can target a number of different viruses or cancer cells in the body.
“So we can use these big, long molecules to put in a lot of sequences to shut down a lot of different proteins at the same time,” he said.
He gives the example of a person who has a cancer cell, which will create oncogenes, which transform the cells into tumor cells.
“If we can get our molecule to target these oncogenes and turn them off, we can stop the cancer cell,” DeWitte-Orr said.
In the lab, his team was able to successfully demonstrate this method in human lung cells infected with SARS-COV-2, the virus that causes COVID-19.
The method has also been successful with other coronaviruses that cause the common cold and has also worked with human brain cancer cells.
“In viruses, we saw up to a 90% drop in virus production,” he said. “And for cancer, we can kill the cancer cell within a day or two.”
Previous research in the area led scientists to put too much dsRNA into a test subject to target cells, which does not replicate a natural response to a virus. Using a smaller amount of the dsRNA better mimics the reaction to a real-life virus, DeWitte-Orr said, and allows for a more controlled response to the virus.
“We could put all the flu sequences for the flu variants that are circulating today, and then we could also add some coronavirus variants in there, and put them into a molecule, you could inhale it and your airways would be protected . against infection,” he said.
Their team is already getting some interest from some outside companies that are interested in partnering with them on the project.
“It’s a paradigm shift, and paradigm shifts in science are always hard to accept at first,” he said. “We’re trained as scientists to be critical thinkers, but now I think we have enough data behind us to say, ‘Yes, there’s a phenomenon here.'”
He has just submitted a grant application to try the dsRNA process on living subjects in preclinical trials. So far, it has only been successful in laboratory dishes. The next step requires moving to more complex systems, which will include preclinical trials in a hamster model with SARS-CoV-2. If successful, it will move on to human trials, a process that could take years.
At the tissue level, it is also embarking on trials for glioblastoma, a rare form of brain cancer.
“Any situation where a cell makes too much of something, you could use our technology in that application,” he said. “This technology has incredible potential, but we can only go as fast as the resources support it. So we need money, because we can only do the research that money will fund.”
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