New investment takes hepatitis B research one step closer to finding a cure

Hepatitis B virus on a white background. 3d illustration

Image: iStock

Melbourne scientists have been awarded $1.7 million over the next five years to advance world-first research into a cure for hepatitis B virus infection thanks to a grant from the mRNA Victoria Activation Program.

The collaborative team is led by the Doherty Institute and includes Monash Institute of Pharmaceutical Sciences, Peter MacCallum Cancer Centre, Royal Melbourne Hospital and St Vincent’s Hospital.

Chronic hepatitis B disease, caused by the hepatitis B virus (HBV) infection, remains a significant worldwide public health issue, with an estimated 296 million people chronically infected including over 226,000 Australians.

There is no cure for chronic hepatitis B disease. Current treatment can reduce the progression of liver disease by stopping the virus from replicating, however treatment is lifelong and does not fully eliminate the risk of liver cancer. New approaches to treat and cure HBV infection are needed.

The Royal Melbourne Hospital’s Dr Margaret Littlejohn is a Senior Medical Scientist in the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute. She is the Chief Investigator of a research project looking to develop a new RNA-based therapy for chronic hepatitis B.

“Chronic hepatitis B hasn’t been cured so far in part because current therapies have failed to destroy the reservoir of viral DNA, where the virus hides in the cells of the liver,” Dr Littlejohn explains.

Using CRISPR technology, a highly significant new technique that allows scientists to modify or destroy targeted DNA sequences, Dr Littlejohn’s team has already made some promising discoveries, in collaboration with scientists at Peter MacCallum Cancer Centre.

“Our PhD student Laura McCoullough has developed a new potential treatment against HBV infection that reduces HBV replication in laboratory cell culture models,” Dr Littlejohn said.

“But the viral reservoir in the cells in the liver was not impacted by this approach."

To address this, the researchers will also specifically target the viral DNA reservoir.

“This means we can target the complete HBV life cycle, the first such project to do this worldwide, and we plan to deliver these treatments to the liver as RNA molecules in lipid nanoparticles, similar to the technology used in COVID vaccines,” Dr Littlejohn explained.

“Our work will pave the way for clinical studies that may lead to a new HBV therapy, benefiting all who currently live with chronic HBV infection,” said the Royal Melbourne Hospital’s Professor Peter Revill, Head of Molecular Research & Development at VIDRL at the Doherty Institute.

Professor Colin Pouton from the Monash Institute of Pharmaceutical Sciences said the collaborative project is testament to the pool of exceptional talent in RNA research right here in Victoria.

“We’re grateful to mRNA Victoria for their ongoing commitment to local RNA capability, and very much look forward to working alongside this fantastic team to advance research into a cure for HBV,” said Professor Pouton.

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Investigators:

Dr Margaret Littlejohn, Senior Scientist, Victorian Infectious Diseases Reference Laboratory (VIDRL), Royal Melbourne Hospital, and Department of Infectious Disease, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity (Doherty Institute)

Professor Peter Revill, AM, Head Molecular Research & Development, VIDRL, Royal Melbourne Hospital and Department of Microbiology and Immunology, University of Melbourne, at the Doherty Institute

Laura McCoullough is a PhD student at VIDRL, supervised by Dr Littlejohn and Prof Revill, and part of the Department of Microbiology and Immunology, University of Melbourne at the Doherty Institute

Dr Mohamed Fareh, Senior Research Fellow in the Cancer Immunology Program, Peter MacCallum Cancer Centre

Professor Joe Trapani, Head, Cancer Immunology Program, Peter MacCallum Cancer Centre

Dr Jacinta Holmes, Gastroenterology Fellow, St Vincent’s Hospital

Professor Colin Pouton, Professor of Pharmaceutical Biology, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University

Professor Damien Purcell Professor of Virology and Laboratory Head, Department of Microbiology and Immunology at the Doherty Institute

Dr Paula Ellenberg is an early career researcher in CI Purcell’s group in the Department of Microbiology and Immunology at the Doherty Institute