GoKawiilA wave of epigenetic therapies is offering hope as ways to cure chronic hepatitis B — a lingering liver infection that is caused by the hepatitis B virus (HBV) and affects more than 250 million people around the world. Currently available drugs often fail to eradicate the virus from the body.
Gene-editing therapies — which make cuts to the DNA strands — have been explored but for hepatitis B, they can increase cancer risks. Researchers are turning instead to epigenetic editing, which modifies markers attached to the DNA to alter how genes are turned on and off.
Scientists working at the biotechnology firm nChroma Bio in Boston, Massachusetts, and at institutes in Milan, Italy, have now placed chemical tags onto the HBV genome to shut down its gene activity and prevent it from producing viral particles. They achieved promising results in experiments on human liver cells and in mice, and the therapy generated only minimal and temporary side effects when tested in monkeys. The study was published in Nature Biomedical Engineering on 21 September1.
‘Epigenetic’ editing cuts cholesterol in mice
The efficacy of a single injection was “quite impressive”. This “is really where we need to go to end up being able to address this pandemic of HBV around the world”, says John Tavis, a molecular virologist at Saint Louis University in Missouri.
The preclinical findings “supported clinical advancement of this approach”, says study co-author Angelo Lombardo, a molecular biologist at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. nChroma Bio has now launched a clinical trial to test multiple doses of the treatment in Hong Kong and New Zealand. The first participant received the therapy, through an intravenous infusion, in January.
The trial in humans is “a huge step” and “a realization of many, many years of work”, adds Lombardo, who co-founded nChroma Bio but does not have an official role at the firm. nChroma Bio declined Nature’s request to comment on the study.
Targeting hidden copies
HBV infections can turn into life-long challenges because the virus has ways to remain in the body and trick the immune system into not fighting against it. One of these is making free-ranging mini-chromosomes that can hide inside liver cells for a very long time.
These twists of viral DNA form “a genomic archive of the virus”, which help it to replicate when people stop taking anti-HBV drugs and lead to a severe rebound of the disease, explains virologist and clinical hepatologist Fabien Zoulim at the University of Lyon in France. Less than 10% of people who are treated for HBV for at least 10 years can cease their daily medications without such risk, Zoulim adds.
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