A team of 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.
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 Hepatitis B 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 (RMH) 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 Institute.
“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 lifecycle, 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 RMH's Professor Peter Revill, Head of Molecular Research & Development at VIDRL at the Doherty Institute.
Dr Margaret Littlejohn, Senior Scientist, Victorian Infectious Diseases Reference Laboratory (VIDRL), the RMH, and Department of Infectious Disease, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity (Doherty Institute)
Prof Peter Revill, AM, Head Molecular Research & Development, VIDRL, the RMH 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
Prof Joe Trapani, Head, Cancer Immunology Program, Peter MacCallum Cancer Centre
Dr Joan Ho is an early career researcher at the Monash Institute of Pharmaceutical Sciences, Monash University, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
Dr Jacinta Holmes, Gastroenterology Fellow, St Vincent’s Hospital
Prof Colin Pouton, Professor of Pharmaceutical Biology, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
Prof 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