New Method for "Silencing" RNA Against Hepatitis B Emerges

Mirus Bio, a spinoff company from the University of Wisconsin-Madison, has developed a method for “silencing” RNA against hepatitis B (HBV) that has reached clinical trials in Asia, Europe, and the United States, according to a press release.

Mirus Bio is a company that was founded by Jon Wolff, an internationally renowned gene specialist and head of the UW-Madison Department of Pediatrics lab, that has expanded from performing basic research to the development of products; they invented the silencing technique that is being used by Arrowhead Pharmaceuticals. Arrowhead Pharmaceuticals’ slogan is to “Target the Gene, Silence the Disease,” with its main focus lying in the development of innovative drugs to treat genetic-based diseases, according to their website. The technique was proved to be effective through the use of technology that was licensed from the Wisconsin Alumni Research Foundation.

According to the World Health Organization (WHO), around 240 million people are chronically infected by HBV and complications from the infection (including liver cancer and cirrhosis) are responsible for 686,000 deaths each year. HBV remains a public health concern worldwide even though there are effective vaccines that prevent the infection and in some cases, the immune system is able to eliminate the infection even without the aid of a vaccine, according to the press release.

However, David Lewis, chief scientific officer at Arrowhead Pharmaceutical’s research facility in Madison noted that in 10% of HBV cases, “the virus produces proteins that dampen the immune response, allowing those infections to become chronic.”

Arrowhead Pharmaceuticals “is in the midst of a private stock offering” that aims to raise $45 million dollars to put towards the advancement of the HBV drug (ARC-520 and ARC-521) as well as a drug that will treat alpha-1 antitrypsin deficiency, a liver and lung disease that is inherited.

According to the website, ARC-520 and ARC-521, “silence all HBV gene products and intervene upstream of the reverse transcription process where current standard-of-care nucleotide and nucleoside analogies act.” They continue on to say that they believe that these therapies will allow the immune system to eliminate the virus and lead to a functional cure for HBV.

When speaking of their approach, Lewis said, “Our strategy is to use RNAi to decrease the production of the viral proteins that weaken the immune system, allowing it to recover to the point that it will be able to clear the virus like it does in the other 90 percent of people who become infected.”

First discovered in 1998, RNA interference was thought to be the answer to fighting disease due to the idea that scientists could use RNA to “shut down problematic genes,” according to the press release. This original plan for RNA has not been brought to fruition yet; RNAi medicine has not yet received FDA approval and reached the market, although two have finally reached the final phase of clinical trials.

The strands of RNA in RNAi are designed to either clog up the unwanted RNA rendering it unable to produce protein, or they are designed to target the unwanted RNA and eliminate it completely. Lewis described how RNAi splits the messenger RNA as a “natural process.” Lewis added, “Almost all cells have this capability. It’s another level of control over gene expression.” When it comes to gene expression, the process is that DNA creates RNA and RNA creates protein, according to the press release.

The strands of RNA that had been injected into the body in the early developmental stages of RNAi were not found to be very beneficial in that the strands ended up excreted through urination. However, Lewis and his team have created a system that connects an RNA strand to a molecule that can latch onto liver cells, thus making strides when it comes to potential treatment for liver disease.

Arrowhead Pharmaceuticals, where Lewis currently works, is in the process of developing other RNAi drugs, but the majority of its effort lies in advancing towards dosing level, phase 2 trials, for HBV. Currently, the drug is being tested at a variety of different dosing schedules as well as being combined with other antiviral drugs.

Lewis stressed, “This drug will not, by itself, clear the virus. That’s the job of the immune system. Even if they still have viral DNA hiding somewhere, now the immune system can recognize a call that produces viral antigens and destroy it.”