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CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, is a revolutionary gene-editing technology that allows scientists to make precise changes to DNA and RNA. In a study led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) in partnership with the Peter MacCallum Cancer Centre, researchers have, for the first time, programmed CRISPR-Cas13b to target the RNA of the hepatitis B virus (HBV) to curb the virus’ replication. This innovative approach has shown promising results, as detailed in the Journal of Hepatology.

Affecting over 296 million people worldwide, chronic hepatitis B infection is a leading cause of liver cancer globally. Existing antiviral treatments, which are often life-long and can lead to adverse effects, help control the virus but cannot cure it or eliminate it from the body. The global scientific community has unanimously recognised the pressing need for new, effective therapeutic approaches that target different stages of the HBV lifecycle.

The Royal Melbourne Hospital’s Dr Laura McCoullough, a Medical Scientist at the Doherty Institute and first author of the study, described the impact of CRISPR-Cas13b technology on HBV.

"CRISPR-Cas13b works like a pair of molecular scissors, cutting the RNA that HBV needs to replicate,” said Dr McCoullough.

“Using this technique in the laboratory, we managed to significantly reduce the levels of HBV proteins, usually found in the blood of individuals living with HBV, by an impressive 96 per cent. This is an excellent outcome given high levels of these proteins often indicate greater risks of liver disease progression and complications.”

Dr Mohamed Fareh and Professor Joe Trapani, experts in CRISPR-Cas13 at the Peter MacCallum Cancer Centre, said the technology presents significant potential for a variety of viruses.

“CRISPR-Cas13b is a promising programmable antiviral tool capable of specifically targeting HBV RNA, crucial for its replication, without harming the patient's own genetic material,” said Dr Fareh.

“What excites us is the adaptability of this technology. We can repurpose it to target not only HBV but also other dangerous viruses and cancer-causing RNAs. This versatility offers hope for developing new treatments across a range of diseases,” added Professor Trapani.

The Royal Melbourne Hospital’s Professor Peter Revill, Head of Regional and Global Health at VIDRL at the Doherty Institute, co-founder of the International Coalition to Eliminate Hepatitis B (ICE-HBV) and senior author of the paper, underscored the significance of their research in advancing HBV treatment.

“Several CRISPR technologies have been used to target HBV with varying degrees of success. Our study marks a milestone in HBV research by demonstrating, for the first time, the effectiveness of targeting HBV RNA using CRISPR technology,” said Professor Revill.

“This approach showed remarkable results, potentially opening the door to a more effective treatment strategy for chronic HBV which may pave the way to a cure, ultimately improving patient outcomes and quality of life.”

Peer review: McCoullough L, et al. CRISPR-Cas13b-mediated suppression of hepatitis B virus replication and protein expression. Journal of Hepatology (2024). https://doi.org/10.1016/j.jhep.2024.05.025

Collaboration: Royal Melbourne Hospital, Victorian Comprehensive Cancer Centre - Peter MacCallum Cancer Centre, Monash Institute of Pharmaceutical Sciences, St Vincent’s Hospital.

Funding: The Australian Centre for HIV and Hepatitis Virology Research, National Health and Medical Research Council (NHMRC), North Brighton Rotary Group and mRNA Victoria.

Useful links: 

• WHO CC for Viral Hepatitis - https://www.doherty.edu.au/viralhepatitis
• Our Work, Hepatitis - https://www.doherty.edu.au/our-work/institute-themes/viral-infectious-diseases/hepatitis/summary
• Podcast, The A to E of Hepatitis - https://www.doherty.edu.au/news-events/podcast/the-a-to-e-of-hepatitis-what-you-need-to-know