Express for chronic hepatitis B virus infection, single-base editing technology shows functional healing potential

▎Editor of WuXi AppTec's content team recently, Beam Therapeutics announced that its preclinical research results showed that its cytosine base editor (CBE) in an in vitro model reduces the expression of hepatitis B virus surface antigen (HBsAg) and prevents the level of hepatitis B virus from falling The potential for rebound after antiviral drugs are stopped
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Chronic hepatitis B virus (HBV) infection can increase the risk of life-threatening health problems such as liver cirrhosis, liver failure, and liver cancer
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A hallmark of chronic hepatitis B infection is the persistent presence of covalent circular DNA (cccDNA) in the nucleus of liver cells
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And hepatitis B virus DNA can be integrated into the genome of the infected cell
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Although current antiviral therapies can control HBV replication, they cannot eliminate cccDNA
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Can not stop due to HBV cccDNA level rally is one of the key challenges need to be addressed to cure hepatitis
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Image source: The base editor of Beam's official website can convert a specific base into another base without causing a double-strand break
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In HBV-infected cells, CBE can accurately introduce stop codons in multiple positions of cccDNA, thereby inhibiting viral gene expression
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▲The strategy of using base editing to functionally cure hepatitis B (picture source: Beam Therapeutics official website) In in vitro experiments, researchers screened out two guide RNAs (gRNAs) targeting the HBV genome, and used them to mediate the HBV genome Stop codons are introduced at different positions
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Experimental results showed that the use of base editing successfully reduced the expression of HBsAg and HBeAg protein, as well as the DNA and RNA levels of HBV
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The efficiency of base editing is 30%-60%
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▲Base editing successfully reduced a variety of HBV viral indicators (picture source: Beam Therapeutics official website).
Combining base editing with the standard antiviral drug lamivudine further increased the base editing efficiency by 20%, resulting in a higher antiviral effect
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Moreover, in the long-term HBV-infected primary hepatocyte culture, the combination of single-base editing and lamivudine can prevent the rebound of the virus level after the withdrawal of lamivudine
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▲Single-base editing prevents the rebound of virus levels after lamivudine is stopped (picture source: Beam Therapeutics official website) Based on this result, Beam plans to conduct a proof-of-concept study on the base editing treatment of chronic hepatitis B in an in vivo model
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Reference: [1] Beam Therapeutics Announces Preclinical Data Highlighting Potential of Base Editors to Target Disease Drivers of Chronic Hepatitis B Infection.
Retrieved September 28, 2021, from https://investors.
beamtx.
com/news-releases/news-release -details/beam-therapeutics-announces-preclinical-data-highlighting[2] cccDNA inactivation using cytosine base editors.
Retrieved September 28, 2021, from https://beamtx.
com/wp-content/uploads/2021/09/cccDNA -inactivation-using-CBE_final.
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The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
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This article is not a treatment recommendation either
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