Project: Pre-clinical investigation of CRISPR-Cas13b as a novel therapeutic approach for hepatitis Delta virus (HDV).
Revill Group
Chronic hepatitis B disease caused by infection with hepatitis B virus (HBV) affects over 296 million people worldwide, including 240,000 Australians. More than 880,000 people die each year directly from HBV related causes, including end-stage liver disease with cirrhosis, liver failure and liver cancer. There is no cure.
Hepatitis Delta virus (HDV) coinfection with HBV causes the most serious form of liver disease and treatment options are extremely limited for the estimated 70 million people worldwide living with chronic HDV infection. There is no cure for chronic HDV. HDV is a satellite virus of hepatitis B virus (HBV), utilizing the envelope proteins of HBV to infect cells. However, it does not require other HBV proteins for replication.
Our group has recently shown that CRISPR-Cas13b can be repurposed to target HBV RNA, greatly reducing HBV replication in cell culture. Since the genome of HDV is RNA, we propose that Cas13b can also be repurposed to target HDV RNA, to reduce HDV replication. In this project we will design specific sequences known as guides, that will bind to the HDV RNA in cell culture, targeting it for Cas13b mediated cleavage. If successful, this may form the basis of a new therapy for chronic HDV.
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Revill Group
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The Revill group focuses on developing new approaches towards HBV cure and understanding the mechanisms by which HBV causes liver cancer. His team utilises a range of in vitro and in vivo models to investigate novel therapeutic approaches (bio-nanoparticles) and the contribution of HBV genotypes and sequence variants to observed differences in HBV replication, disease progression and treatment response. Peter's team focuses on 2 main approaches towards HBV cure: (i) Using CRISPR-Cas to control HBV an hepatitis delta virus (HDV) replication and protein expression and (ii) using virus like particles to trigger immune responses that will naturally cure HBV infection. His group also investigates the role of HBV splice variants, which his team has shown may be predictive of liver cancer. Peter’s team has also pioneered the use of deep sequencing and novel haplotype analysis to identify predictors of treatment response, potential new drug targets, and the likelihood of progression to functional cure on therapy.
Revill Group Current Projects
Research degrees at the Doherty Institute are administered by the University of Melbourne.