Researchers at Boston-based genetic medicines company nChroma Bio published preclinical data in Nature Biomedical Engineering supporting CRMA-1001, an LNP-delivered epigenetic silencer now in Phase I/II development for chronic hepatitis B (CHB). The study showed durable suppression of viral markers from both integrated and episomal HBV DNA without cutting the underlying DNA sequence.
Why it matters: Current nucleoside/nucleotide analogue therapies suppress HBV replication but do not eliminate or durably silence the cccDNA and integrated HBV DNA reservoirs that sustain chronic infection. CRMA-1001 is designed to switch off transcription from both reservoirs through targeted DNA methylation, potentially enabling durable viral suppression from a finite treatment course.
CRMA-1001 delivers mRNA encoding the EE7000 epigenetic silencer together with an HBV-targeting guide RNA in liver-directed lipid nanoparticles. The complex uses catalytically inactive Cas9 to localize transcriptional repressors and DNA methyltransferase activity to HBV DNA, depositing methylation marks without introducing DNA breaks.
In mouse models, a single dose produced dose-dependent suppression of HBV antigens that persisted for up to 207 days. In an episomal HBV model, three monthly doses left approximately 90% of animals with undetectable HBsAg and HBV DNA at six months. The therapy also suppressed HBsAg and HBeAg in HBV-infected primary human hepatocytes, with methylation of cccDNA confirmed. A non-human primate toxicology program supported clinical entry, although transient liver transaminase elevations were observed at the highest tested dose.
The preclinical package supported progression into a Phase I/II trial (NCT07200193), which dosed its first patient in January 2026. The study is evaluating single and multiple ascending doses in up to 66 adults with CHB who remain on background nucleoside/nucleotide analogue therapy.