Cutting Out Hepatitis B Engineered Meganucleases Designed to Cleave the Virus’s Genome Across Multiple Strains

A US genomic medicine company has patented a class of engineered meganucleases – precision molecular scissors – specifically designed to cut and disable the Hepatitis B virus genome across multiple viral genotypes. The invention represents a potentially curative approach to a disease that currently affects hundreds of millions of people worldwide and for which existing treatments suppress but rarely eliminate the virus.

The Problem

Hepatitis B virus (HBV) infection is a global health crisis of enormous scale. An estimated 296 million people worldwide are living with chronic HBV infection, and the virus kills approximately 820,000 people each year through cirrhosis and liver cancer (hepatocellular carcinoma). Despite decades of research, a true cure – one that eliminates the virus from infected cells – remains elusive.

Current antiviral treatments for chronic HBV suppress viral replication, reducing the amount of virus in the bloodstream and lowering the risk of liver damage. However, they rarely achieve a functional cure, because the virus persists in the nucleus of infected liver cells in a form called covalently closed circular DNA (cccDNA) – a stable reservoir that antiviral drugs cannot reach. When treatment is stopped, viral replication typically rebounds from this reservoir. Most patients face decades of treatment, with associated costs, side effects and compliance challenges.

A fundamentally different approach – one that directly targets and destroys the viral DNA within infected cells – is needed to achieve lasting cure. The challenge is developing a molecular tool with sufficient precision to target HBV sequences specifically, while being effective across the diverse range of HBV genotypes that infect patients globally.

What This Invention Does

Precision BioSciences’ invention describes engineered meganucleases – large, naturally occurring DNA-cutting enzymes that have been engineered to recognise and cleave specific sequences within the HBV genome. Unlike the CRISPR-Cas9 system that has received widespread attention, meganucleases are single-protein tools that combine DNA binding and cutting activity in one molecule, potentially offering advantages in specificity and delivery.

The engineered meganucleases described in the patent are designed to recognise recognition sequences within open reading frames of the HBV genome that are conserved across at least two HBV genotypes. By targeting sequences common to multiple genotypes, the treatment could be effective across the broad range of HBV strains circulating in patients worldwide, rather than being limited to a specific genetic variant of the virus.

The invention also covers pharmaceutical compositions containing these meganucleases – both as proteins and as nucleic acids encoding them – and their use in treating HBV infections and HBV-related hepatocellular carcinoma.

Key Features

Multi-genotype targeting. The meganucleases are engineered to recognise sequences conserved across multiple HBV genotypes, enabling broad therapeutic coverage across the diverse HBV strains found in patients globally.

Genome-editing mechanism. By cleaving the HBV genome directly – including the cccDNA reservoir that current antivirals cannot address – the meganucleases offer the potential for a true functional cure rather than lifelong viral suppression.

Single-protein architecture. Meganucleases combine DNA recognition and cleavage in a single engineered protein, distinguishing them from multi-component editing systems and potentially simplifying delivery and specificity optimisation.

Hepatocellular carcinoma coverage. The patent explicitly covers the use of these meganucleases in treating HBV-associated liver cancer, reflecting the well-established causal link between chronic HBV infection and hepatocellular carcinoma.

Pharmaceutical composition breadth. Both protein-based and nucleic acid-based (gene therapy) forms of the meganucleases are covered, giving the invention scope across multiple potential delivery modalities.

Who Is Behind It?

Precision BioSciences, Inc. is a Durham, North Carolina-based genomic medicine company known for its ARCUS genome editing platform, which is based on engineered meganucleases. The inventors are Derek Jantz and James Jefferson Smith. This application is a divisional of AU 2023263542, which itself traces back to AU 2017342536 – reflecting an extended development timeline. The application is managed by Davies Collison Cave Pty Ltd in Milton, Queensland.

Why It Matters

HBV infection is heavily concentrated in low- and middle-income countries in Asia and sub-Saharan Africa, where access to long-term antiviral therapy is limited and the burden of HBV-related liver cancer is devastating. A curative treatment – one that could be delivered in a defined course rather than requiring indefinite daily medication – would be transformative for global health equity.

Genome-editing approaches to HBV represent a scientifically compelling path to cure, and the ARCUS meganuclease platform has been advancing through preclinical and early clinical development. With IPC classifications covering endonucleases (C12N 9/22) and pharmaceutical peptide compositions (A61K 38/00), the patent sits at the intersection of molecular biology, virology and therapeutic innovation.

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AU 2026201532 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

Hepatitis B infects approximately 296 million people globally, with the highest burden in Asia and sub-Saharan Africa. Existing antivirals suppress replication but cannot eliminate the cccDNA reservoir that persists in infected liver cells, making lifelong treatment necessary for most patients.

Engineered meganucleases are among several genome editing approaches – alongside CRISPR-Cas9 – being investigated as potentially curative strategies for chronic HBV. Their single-protein architecture may offer advantages in delivery and specificity for targeting the viral genome within infected hepatocytes.