Epigenetic editing silences hepatitis B virus without cutting DNA

Overview

Updated 1 hour ago

A single injection silenced hepatitis B virus in human liver cells and mice by tagging viral DNA with chemical marks instead of cutting it. The therapy, called CRMA-1001, is now in human trials in Hong Kong and New Zealand, with the first participant dosed in January 2026.

Chronic hepatitis B affects more than 250 million people worldwide. Existing drugs suppress the virus but rarely eliminate it, because the virus hides its DNA inside liver cells. This approach aims to switch that DNA off permanently, offering a functional cure without the cancer risk of DNA-cutting gene therapies.

Why it matters

If this works, millions of people with chronic hepatitis B could be functionally cured without the cancer risk of DNA-cutting gene therapies.

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Key Indicators

250M+

People with chronic hepatitis B worldwide

World Health Organization estimate of the global chronic HBV burden.

Participants dosed in CRMA-1001 trial

First participant received the therapy by intravenous infusion in January 2026.

Trial locations

Clinical trial sites in Hong Kong and New Zealand testing multiple doses.

Voices

Curated perspectives — historical figures and your fellow readers.

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People Involved

Angelo Lombardo

Molecular biologist, San Raffaele Telethon Institute for Gene Therapy, Milan

Study co-author; co-founded nChroma Bio but holds no official role there

John Tavis

Molecular virologist, Saint Louis University

Independent commentator on the study

Organizations Involved

nChroma Bio

Biotechnology company

Developer of CRMA-1001; running clinical trial in Hong Kong and New Zealand

Boston-based biotech developing epigenetic therapies for chronic viral infections.

San Raffaele Telethon Institute for Gene Therapy

Research institute

Research partner in the CRMA-1001 study

Milan-based gene therapy research institute affiliated with San Raffaele Hospital and the Telethon Foundation.

Timeline

January 2026 September 2026

2 events Latest: Today

September 2026
Preclinical study published in Nature Biomedical Engineering
Today Publication

Study shows epigenetic silencing of HBV in human liver cells and mice; minimal side effects in monkeys.
Today
January 2026
First patient dosed in CRMA-1001 trial
Clinical Trial

First participant receives CRMA-1001 by intravenous infusion in Hong Kong or New Zealand.
January 2026

Scenarios

CRMA-1001 shows durable viral suppression in early trial data

Likely Resolves by End of 2027

Discussed by: Study authors and nChroma Bio

If the therapy silences HBV DNA as effectively in humans as it did in mice and monkeys, interim trial data could show reduced viral DNA and antigen levels in treated participants. The trial is testing multiple doses, so dose-response data would strengthen the case for advancing to larger trials. The preclinical single-injection efficacy was described as "quite impressive" by independent virologist John Tavis.

Trial reveals safety concerns, therapy paused or redesigned

Unlikely Resolves by End of 2027

Discussed by: Regulatory authorities and clinical trial monitors

The therapy showed only "minimal and temporary" side effects in monkeys, but human immune responses to the lipid nanoparticle delivery system or the CRISPR components could differ. Any serious adverse events would pause the trial and require redesign. The epigenetic approach was chosen partly because nuclease-based gene editing carries cancer risks, so safety scrutiny will be intense.

Miniature CRISPR editors overtake CRMA-1001 in development

Possible Resolves by Q2 2028

Discussed by: Nature Structural & Molecular Biology researchers

A separate team engineered xCas12m, a miniature CRISPR protein small enough to fit in a single AAV vector, and used it to silence HBV in mice. If this approach proves easier to deliver and equally durable, it could become the preferred platform for epigenetic HBV therapy. The xCas12m-CRISPRoff platform achieved durable silencing in a mouse model with a single AAV administration.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

December 2013 - October 2014

Hepatitis C direct-acting antivirals (2013-2014)

Sofosbuvir (Sovaldi) and related drugs transformed hepatitis C from a chronic, progressive infection to a curable one, with cure rates above 90% in many patient groups. The drugs targeted viral enzymes directly, blocking replication.

Then

HCV cure rates soared and liver transplant waitlists shrank within a few years.

Now

HCV went from a leading cause of liver cancer to a largely manageable disease, though access and cost remain issues.

Why this matters now

HCV showed that a functional cure for a chronic viral hepatitis is achievable. But HBV is harder because it integrates into host DNA, which is why epigenetic silencing rather than antiviral drugs may be needed.

October 2016

CRISPR base editing (2016)

David Liu's lab at the Broad Institute developed base editors that make single-letter DNA changes without creating double-strand breaks. This reduced off-target damage compared to standard CRISPR-Cas9 cutting.

Then

Base editing opened new therapeutic possibilities for genetic diseases.

Now

It established the principle that more precise, less destructive genome modification is safer and often more effective.

Why this matters now

Epigenetic editing follows the same logic: instead of cutting viral DNA, which risks cancer, it adds chemical tags that silence gene activity without altering the DNA sequence.

2010s - present

HIV 'block and lock' strategies (2010s-present)

Researchers explored using epigenetic silencing to keep HIV in a latent state, preventing viral reactivation without eliminating the virus. The approach uses drugs or genetic tools to add repressive marks to the HIV genome.

Then

Proof-of-concept studies showed HIV could be silenced in cell models.

Now

The approach remains experimental, but it established the concept of a 'functional cure' for persistent viral infections.

Why this matters now

HBV epigenetic editing applies the same 'block and lock' concept to a different virus, with the advantage that HBV's DNA is more accessible in liver cells than HIV's is in immune cells.