Researchers in Italy and the US have developed a gene therapy that reduced hepatitis B virus (HBV) activity in mice and was found to be safe in monkeys, backing its progression to clinical trials. 

Hepatitis B is a viral infection that affects the liver and is estimated to cause 1.1 million deaths each year, mostly from cirrhosis and liver cancer. Current treatments can control the virus but, partly because viral DNA can persist inside liver cells, the infection can become active again if treatment stops. Some HBV DNA can also integrate into human DNA, where it can hijack cells to produce viral proteins. 

Researchers from the San Raffaele Telethon Institute for Gene Therapy, Italy, and biotech company nChroma Bio, US, developed CRMA-1001, a therapy that uses modified CRISPR gene editing — a tool that can precisely alter DNA sequences — to attach chemical tags to HBV DNA. These tags make viral DNA harder for cells to read, acting like an “off” signal and reducing the activity of viral genes without cutting the DNA.In mice, CRMA-1001 treatment reduced viral DNA and proteins, with 90% of treated animals having undetectable HBV DNA levels six months later. 

The team also gave three monthly doses of CRMA-1001 to healthy cynomolgus monkeys to assess safety. At the highest dose, liver enzyme levels in the blood rose temporarily, indicating a short-term stress in the liver, but returned to normal within four weeks. No other treatment-related adverse effects were reported. A clinical trial will now assess whether the therapy can provide lasting control of HBV infection in people and further evaluate its safety. 

“We look forward to generating early clinical insights that will inform the future development of CRMA-1001 and potentially reshape the therapeutic landscape for chronic hepatitis B,” said Jenny Marlowe from nChroma Bio and lead author of the study published in Nature Biomedical Engineering.