A novel class of epigenetic therapies is emerging as a potential cure for chronic hepatitis B, a persistent liver infection caused by the hepatitis B virus (HBV) that impacts over 250 million individuals globally. While current pharmaceutical interventions often fail to eliminate the virus entirely, gene-editing approaches that sever DNA strands have raised concerns regarding increased cancer risks. Consequently, researchers are pivoting toward epigenetic editing, a method that alters gene expression by modifying chemical markers attached to DNA without cutting the genetic code.
Scientists from the biotechnology company nChroma Bio, based in Boston, Massachusetts, and collaborating institutions in Milan, Italy, have developed a treatment that applies chemical tags to the HBV genome. This process suppresses viral gene activity and halts the production of viral particles. The findings, published on September 21 in Nature Biomedical Engineering, demonstrated strong efficacy in human liver cells and mouse models. Furthermore, tests in monkeys revealed only minor and transient side effects.
The impact of a single injection was described as “quite impressive” by John Tavis, a molecular virologist at Saint Louis University in Missouri. Angelo Lombardo, a molecular biologist at the San Raffaele Telethon Institute for Gene Therapy in Milan and a co-author of the study, noted that the preclinical data strongly supports moving toward clinical applications. He stated that this approach is essential for addressing the global HBV pandemic.
Responding to these findings, nChroma Bio has initiated a clinical trial to evaluate multiple doses of the therapy in Hong Kong and New Zealand. The first human participant received the treatment via intravenous infusion in January. Lombardo, who co-founded nChroma Bio but currently holds no official position there, characterized the human trial as a monumental step and the culmination of years of research. nChroma Bio declined to provide additional comment to Nature.
HBV infections often become lifelong conditions because the virus employs mechanisms to evade the immune system. One such strategy involves creating free-floating mini-chromosomes that reside within liver cells for extended periods. Fabien Zoulim, a virologist and clinical hepatologist at the University of Lyon in France, explained that these structures form a “genomic archive” that allows the virus to replicate rapidly once patients stop taking anti-HBV medications, leading to severe disease rebound. According to Zoulim, fewer than 10% of individuals treated for at least a decade can safely discontinue daily medication without facing this risk.
Additionally, HBV can integrate fragments of its genome into the host’s DNA, producing proteins that modulate the immune response. Zoulim warned that this integration of viral DNA induces molecular changes in liver cells that can predispose patients to cancer.
The nChroma therapy, designated CRMA-1001, utilizes a modified version of the CRISPR-Cas9 enzyme that has been stripped of its ability to cut DNA. Instead, it carries RNA strands that guide the enzyme to specific targets within the HBV genome. Encased in a lipid nanoparticle, the treatment silences both free-ranging and integrated HBV DNA by attaching methyl groups to them.
Gene therapy without the gene scissors—brilliant. I’m cautiously optimistic about these early human trial results.
Wait, so it works in humans but they are just starting trials now? How long until this is widely available?
Monkeys had only minor side effects—this is huge news for the 250 million people living with HBV globally.
I wonder if silencing the virus is enough, or if we really need total eradication to stop liver cancer risk?
Finally, a safe alternative to cutting DNA! This epigenetic approach sounds much less risky for cancer.