A team of researchers at the Näär Lab at UC Berkeley have developed a new inhalable drug that blocks the viral replication of SARS-CoV-2 in lung cells.

The drug is a type of antisense oligonucleotide, or ASO. These are small pieces of DNA or RNA that can bind to RNA strands and stop them from working in various ways. The drug has been tested on mice and hamsters so far, with human trials forthcoming.

“The antisense, or the molecular velcro, made it to the lungs, we verified that,” said Anders Näär, professor of metabolic biology and vice chair of the department of nutritional sciences and toxicology. “It didn’t have any deleterious effects in the lungs, so no inflammation that could cause problems, and indeed we saw up to 100 times lower levels of infection in the mice.”

Näär explained that the particular ASO treatment his group developed targets a structural part of the virus genome rather than targeting a spike protein which other treatments, such as vaccines and the drug Paxlovid, have done. This portion of the RNA is much less likely to undergo mutations. Näär added that this makes the ASO treatment effective against all current variants of the virus and likely against future variants as well.

The targeted structure is also critical to the virus’s replication mechanism, which allows it to spread through the body and infect more cells. Therefore, this treatment is useful in both prevention and treatment of COVID-19, Näär said.

“The molecular velcro is incredibly stable,” Näär said. “It’s a chemically modified short snippet of DNA that can be stored indefinitely in the frozen state. It can be dried, and you can basically resurrect it and put it into a nasal spray and then you’re ready for the next pandemic in a decade.”

Näär emphasized that the drug can be stored at room temperature, which could make it far more accessible in regions without access to refrigeration. It is also noninvasive, so people who are “vaccine hesitant” may be more willing to use it, he added.

Chi Zhu, a postdoctoral researcher in the lab, explained that the ASO is also resistant to DNAse and RNAse enzymes and, unlike current pills, doesn’t degrade quickly. This means that rather than multiple doses a day, this treatment may only require one dose a day.

Zhu elaborated that a single dose showed immunity for up to a week in animal trials, though clinical trials will be needed to determine the timescale for humans.

Zhu also explained that the manufacturing process for ASOs is very similar to primers that are widely used in biological science, so scaling up manufacturing would be relatively easy.

“We have been working using ASOs for 13-14 years,” Näär said. “We simply just took this same logic and applied it to the virus and it really works amazingly well.”