Innovative Approach Targets Hepatitis B Virus Using RNA Interference Therapy

Hepatitis B virus remains a significant global health challenge, causing over one million deaths annually due to chronic infections leading to liver damage, cirrhosis, and liver cancer. Despite widespread vaccination efforts and existing treatments, a definitive cure continues to elude scientists. The virus’s stubborn nature allows it to persist and resurface even after treatment, especially in individuals infected during infancy, with some viral DNA integrating into the host’s genome.

Recent research published in Science Translational Medicine highlights promising advancements in using RNA interference (RNAi) therapeutics to combat chronic HBV infections. These drugs work by silencing viral antigens, preventing the virus from replicating and boosting the immune system's ability to fight the infection. The innovative approach is most effective when used in combination with other antiviral drugs.

Dr. John Tavis, a professor of microbiology and immunology at Saint Louis University, explains that a "functional cure" aims to eradicate the virus’s DNA and eliminate the surface antigen—an abundant viral protein—persisting in the bloodstream for at least six months after treatment. Achieving this would mean the virus is unlikely to return and the patient's health risks are minimized to levels comparable to those who have naturally cleared the infection.

However, a true cure remains complex. Infections acquired in adulthood often clear spontaneously, but some residual viral DNA can remain dormant, and in immunosuppressed individuals, the virus can reactivate. Additionally, part of the viral DNA becomes permanently inserted into the host’s genome, which can still produce viral proteins and possibly lead to cancer.

Scientists are developing a multifaceted strategy to reach a functional cure. This involves combining drugs that inhibit viral replication, suppress production of viral antigens, and stimulate the immune system. Some RNAi drugs, such as Bepirovirsen by GlaxoSmithKline, demonstrate the ability to suppress HBV for months even after stopping therapy and activate immune responses.

The goal is to turn off the virus's defenses—its antigens—while encouraging the body's immune system to combat the infection effectively. Data from ongoing clinical trials are promising, with some combination therapies curing about 30% of patients after a year to a year and a half of treatment, a notable improvement over standard care.

While there is still work to be done, these developments suggest that a functional cure for hepatitis B could eventually become a reality, saving millions of lives worldwide and reducing the transmission of this persistent virus.