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RNA Interference Therapy for Chronic Hepatitis B Predicts the Importance of Addressing Viral Integration When Developing Novel Cure Strategies
Christine I Wooddell 1 , Adam J Gehring 2 , Man-Fung Yuen 3 , Bruce D Given 1
Affiliations
Affiliations
1
Arrowhead Pharmaceuticals, 502 South Rosa Road, Madison, WI 53719, USA.
2
Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
3
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
PMID: 33808298 DOI: 10.3390/v13040581
Abstract
Chronic hepatitis B infection remains a globally important cause of morbidity and mortality and has recently undergone a renaissance in therapeutic interest with increased pre-clinical and clinical testing of new drug classes. One of the first new classes in the clinic was RNA interference agents, which have the potential to impact the entire viral life cycle by reducing all virus-produced mRNA. Early clinical testing with the first of these agents in the clinic, ARC-520, demonstrated that rapid and deep reductions in viral proteins, RNA and DNA could be produced with this approach, but also the surprising insight that HBsAg production from incomplete HBV DNA integrated into the host genome appears to play a heretofore unappreciated and important role in maintaining circulating HBsAg, thought to play a fundamental role in preventing host clearance of the virus. Thus, accounting for viral DNA integration in novel HBV treatment approaches may prove to be essential to achieving successful finite therapies of this difficult to treat chronic infection.
Keywords: HBsAg reduction; HBsAg seroclearance; functional cure; hepatitis B treatment; short interfering RNA.
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发表于 2021-4-4 10:50
