UC Berkeley News Press Release:
Berkeley, Calif. – Scientists at the University of California, Berkeley, have created a new remedy for COVID-19 that could one day make treating SARS-CoV-2 infections as undeniable as using a nasal spray for allergies.
The remedy uses short extracts of artificial DNA to erase the genetic machinery that allows SARS-CoV-2 to reflect off the body.
In a new paper published online in the journal Nature Communications, the team shows that those short extracts, called antisense oligonucleotides (ASOs), are highly effective at preventing the virus from replicating in human cells. When administered through the nose, those ASOs are also effective. in the prevention and treatment of COVID-19 infection in mice and hamsters.
“Vaccines make a big difference, but vaccines are not universal and there is still a great need for other approaches,” said Anders Näär, a professor of metabolic biology in UC Berkeley’s Department of Nutritional Sciences and Toxicology (NST) and senior author. of paper. ” A nasal spray that is cost-effective and can prevent someone from becoming inflamed or prevent serious illness can be incredibly helpful. “
Because the ASO remedy targets a component of the viral genome that is highly conserved among the other variants, it is effective against all “troubling variants” of SARS-CoV-2 in human cells and animal models. It is also chemically sound and relatively affordable for large-scale production, making it ideal for treating COVID-19 infections in spaces around the world that do not have access to electric power or cooling.
If the remedy proves safe and effective in humans, ASO generation can be seamlessly changed to target other RNA viruses. The study team is already looking for a way to use it to disrupt flu viruses, which also have pandemic potential.
“If we can design ASOs that target entire viral families, when a new pandemic emerges, as long as we know which circle of relatives the virus belongs to, we can use nasally administered ASOs to suppress the pandemic in its early stages. “The study said. First Chi Zhu, postdoctoral researcher at NST at UC Berkeley. “That’s the beauty of this new treatment. “
Like DNA, RNA carries a genetic form encoded in a series of bases; however, unlike DNA, RNA comes in an unmarried strand, without a complementary moment strand to shape a double helix. However, RNA still gently binds to series of complementary base pairs. short strands of lab-made DNA-like molecules that, like molecular Velcro, are programmed to adhere to and express RNA series in viruses and cells.
For more than a decade, Näär and his team have been reading how those molecules can be used to adjust messenger RNA and microRNA activity in the human body, which could reverse situations such as obesity, type 2 diabetes, fatty liver disease and Duchenne disease. muscular dystrophy. When the COVID-19 pandemic hit, his team temporarily mobilized to investigate whether ASOs can also be used to interfere with SARS-CoV-2.
“The SARS-CoV-2 genome is a single-stranded RNA, similar to messenger RNA or microRNA,” Näär said. “We have the idea that we could use those ASOs to attach to viral RNA and prevent it from working. “
In collaboration with associate professor Sarah Stanley’s lab at UC Berkeley and scientists at the Institute for Innovative Genomics, the team began comparing the SARS-CoV-2 virus with many other ASOs. Each of those ASOs is designed to affect another region. of viral RNA, adding the region encoding the so-called spike protein that is helping the SARS-CoV-2 virus sequester host cells.
Of all those goals, they knew one that is by far the most effective at disrupting the virus. This target is a non-coding series of viral RNA that bureaucratizes a fork loop design and appears to play a key role in aiding SARS-CoV-2 replication. .
“We showed that if you link an ASO to that fork, it dissolves the RNA fork and bureaucracy into a direct line rather than a bubble structure,” Näär said. “This prevents the virus from translating and replicating effectively, and we found that it was incredibly effective in preventing viral replication in human cells. “
When they administered ASOs to the noses of hamsters and inflamed mice, the team found that they were also very effective in preventing and treating COVID-19 infections. It should be noted that those experiments also showed that ASOs did not appear to stimulate a significant immune system. response, indicating that ASOs probably do not produce poisonous side effects in humans.
Since the fork loop design is found in all known variants of SARS-CoV-2, ASOs are effective for everyone. the highly infectious Omicron.
“[SARS-CoV-2] enters the frame and hijacks our own devices to become a copy device to produce tons of copies of viruses for further infection and spread,” the exam said Justin Lee and a graduate student at UC Berkeley NST, in one winner. Graduated from UC. Let’s talk about clicks. ” We were able to locate the key code in the viral RNA that allows the photocopier to work, and all variants, adding Delta and Omicron, share the same key code. “
According to Näär, the team already knew of another ASO target that is discovered in the genetic code of all viruses in the SARS family, adding the SARS-CoV-1 virus that caused the 2002 SARS outbreak. A “cocktail” of those two ASOs may be even more effective at suppressing the virus, and it would be almost as if a new variant escaped.
The team has more experiments to conduct before the ASO remedy is approved for human clinical trials. However, Näär is confident that the remedy will one day be used as part of a variety of remedies for COVID-19 and other viral diseases.
“It’s very transparent that this virus is going away,” Näär said. “We want many other avenues to deal with it, and treatments like ours, which are independent of the variant, can play a major role. “
Other co-authors come with Jia Z. Woo and Silvi Rouskin of the Whitehead Institute for Biomedical Research; Lei Xu, Xammy Nguyenla, Livia H. Yamashiro, Scott B. Biering, Erik Van Dis, Federico Gonzalez, Douglas Fox, Eddie Wehri, Julia Schaletzky, Eva Harris and Sarah Stanley of UC Berkeley; Fei Ji and Ruslan I. Sadreyev of Massachusetts General Hospital; Arjun Rustagi, Benjamin A. Pinsky and Catherine A. Blish of Stanford University; Charles Chiu of the University of California, San Francisco; and Sakari Kauppinen of Aalborg University, Denmark.
This study funded in part through Fast Grants and the Innovative Genomics Institute.
This press release is produced through UC Berkeley News. The perspectives expressed here are those of the author.
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