RNA Silencing Therapy Reduces SARS-CoV-2 Particles In Mouse Lungs By 99.9 Percent

A novel technique to prevent viruses replicating has demonstrated almost complete efficacy against COVID-19 in the lungs of mice. Better yet, it should not only work against all varieties of SARS-CoV-2, but is also expected to work against related coronaviruses such as SARS and MERS. If the work translates to humans, it could mean we are ready for whatever new coronavirus bats are cooking up.

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Professor Nigel McMillan of Griffith University told IFLScience his team have been working on using gene-silencing RNA technology since long before COVID-19 appeared. Known as small-interfering RNA (siRNA) this approach slices up the virus genome, preventing it from replicating. “We started out on viruses that cause cancer, such as human papillomavirus (HPV),” McMillan said.

The team also developed lipid nanoparticles that can carry the siRNA through the bloodstream to the organs where the virus presents a threat, demonstrating the capacity to reduce tumors in mice. Despite the likelihood that the technique could be used to treat cervical cancer, McMillan's team have not found a commercial partner to test its safety and effectiveness in humans.

However, all this previous work (including research on silencing the rare but very deadly Hendra virus) meant that when COVID-19 appeared McMillan was ready to go.

In Molecular Therapy McMillan and co-authors have announced the fruits of that labor, cutting viruses in the lungs of COVID-19 infected mice by 99.9 percent without apparent side effects.

McMillan injected the mice with siRNA-bearing nanoparticles the same day they were infected with the virus, followed by booster shots. Consequently, he admitted to IFLScience, the work does not answer the question of how well the therapy would work on someone admitted to hospital with advanced-stage symptoms. However, McMillan is hopeful. “It takes just 20 minutes for the particles to start leaving the bloodstream,” he told IFLScience.

Although the research focused on the rodents' lungs, previous studies demonstrate the nanoparticles deliver their payloads to most of the other organs COVID-19 has been shown to damage, including the heart and liver. “Everywhere except the brain and maybe the nerves,” McMillan told IFLScience. SARS-CoV-2's capacity to replicate in the brain is thought to contribute to Long Covid, but McMillan noted; “The mice survive quite happily.”

At least one team has demonstrated the siRNA's potential against COVID-19 before, but they used a nasal delivery system which McMillan says breaks down once an infection takes hold.

“We have also shown that these nanoparticles are stable at 4°C for 12 months and at room temperature for greater than one month, meaning this agent could be used in low-resource settings to treat infected patients,” McMillan said in a statement.

The research was one of ten projects funded by the Australian Government as part of a program where the most promising will receive funding for phase I clinical trials. “We're putting our hands up for that,” McMillan said. “Then we will be looking to partner up for phase II and III. With the great clinical need we would certainly expect there to be a lot of interest.”

Even if all phases succeed it will be years before the treatment is available. Nevertheless, McMillan thinks there will still be demand. “COVID is not going away,” he told IFLScience. Moreover, with the RNA targeting a part of the virus McMillan said “hasn't changed in 3000 years,” it should prove effective against many related viruses, including those yet to infect humans

Meanwhile the same gene silencing approach is waiting to be tested against a wide array of other viruses.

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