“We’re really excited about some of these RNAis because they seem to have two modes of action, both suppressing the viral antigens and turning on the immune system. There is a particular drug we reviewed, Bepirovirsen by GlaxoSmithKline, that not only suppresses HBV for many months, even after the drugs are stopped, but it also has a second mechanism that triggers the immune system to go in and help with the job.”
In a recent paper published in Science Translational Medicine, scientists report that a class of drugs called RNA interference (RNAi) therapeutics represent a major advancement in the treatment of chronic HBV infections, expanding treatment strategies by addressing viral antigens, silencing the virus and helping to reinvigorate the body’s immune response. The drugs will most likely be given to patients in combination with other medications, and researchers hope that their addition to drug combination therapies will bring us closer to a functional cure.
The paper’s authors say a functional cure could likely be reached using several drugs together in combination therapies. In addition to replication inhibitors, which stop the virus from making more copies, they are especially enthused by drugs that interfere with viral antigen production. A third arm of the approach would tap drugs that stimulate the immune system to enlist the body’s support in fighting off the virus. Researchers believe that between 20% and 40% of those with chronic HBV infection will die from it if they do not receive treatment, usually from liver failure or liver cancer. A progressive disease that lingers for decades, hepatitis B causes half of all liver cancer cases and it erodes quality of life, causing liver fibrosis and cirrhosis.
“A functional cure means eliminating the viral DNA and a viral protein called the surface antigen, which accumulates in high levels in the bloodstream, for at least six months post-therapy,” said John Tavis, Ph.D., professor of molecular microbiology and immunology at Saint Louis University School of Medicine and one of the paper’s authors.
Doctors and scientists would be elated to be able to offer their patients a functional cure. Even so, they don’t describe this as a true cure, for two reasons.
“Ninety-five percent of people who catch HBV as an adult will get a mild case of hepatitis and then clear it,” Tavis said. “But, even those people sometimes maintain some replication-competent virus in their body. And if they’re immunosuppressed, it can come roaring back. That’s one aspect that prevents it from being really a true cure. The other aspect is that when a person is infected with HBV, some of its viral DNA is permanently inserted into a person’s DNA. Though that fragment isn’t capable of replicating, it can still produce some viral antigens, and it can be cancer-causing.”
Nevertheless, a functional cure would save millions of lives and ultimately limit the spread of the virus. And, researchers believe we may be closing in on a strategy to reach it.
Source: https://medicalxpress.com/news/2025-07-scientists-block-viral-rna-aiming.html
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