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▎Editor of WuXi AppTec content team
Beam Therapeutics today announced the latest preclinical positive data
for its multi-base editing platform.
The results show that this platform can significantly reduce the level of hepatitis B virus (HBV) surface antigen (HBsAg) and other viral biomarkers, and in vivo models can avoid hepatitis B virus replication and viral volume rise, with the potential to become a new treatment
for hepatitis B cure.
Detailed research data was published at the 2022 International Conference on Hepatitis B Virus
.
The hepatitis B virus can cause severe liver infections and chronic diseases, increasing the risk of
life-threatening conditions such as cirrhosis, liver failure, or liver cancer.
Hepatitis B virus produces a unique, free covalently closed loop DNA (cccDNA) in the nucleus of the patient's hepatocytes, which is the template for virus replication, so the content of cccDNA in patients becomes an important indicator
of treatment and disease evaluation of hepatitis B patients.
Hepatitis B virus DNA can also be integrated into the genome of cells and become one
of the sources of hepatitis B surface antigen.
Current liver treatments can limit the replication of hepatitis B virus, but it cannot remove these hepatitis B gene components, which is the cause of repeated infection and recurrence of the virus, and it is also a challenge
in hepatitis B treatment.
Base editing is a technology that changes specific DNA bases in a direct, irreversible way without causing a double-strand break in DNA
.
The cytosine base editor (CBE) can be edited at multiple sites of hepatitis B virus DNA within the human genome as well as free cccDNA, precisely implanting permanent stop codon sequences
in the viral genome.
In contrast to nuclease editing systems, which cause double-stranded DNA breaks, base editing can stop the expression of viral genes without avoiding the
risk of chromosomal recombination.
▲The strategy of base editing therapy to functionally cure hepatitis B (Source: Beam's official website)
The published data is based on previous experimental data, that is, the cytosine base editor developed by Beam, which can successfully implant a stop codon in hepatitis B virus DNA in vitro, resulting in a significant decrease in the biomarker content of hepatitis B-related viruses (including HBsAg, HBeAg, HBV DNA, 3.
5kb RNA).
Based on these findings, Beam further used a mouse model of hepatitis B virus to deliver 1 or 2 doses of cytosine base editors through lipid nanoparticles (LNPs) into mice, and examined the efficacy
of treating hepatitis B with the antiviral drug entecavir as a control group.
Data analysis showed that these two doses of base-editing therapy could cause a sustained decrease in hepatitis B virus surface antigen >2 log10 IU/ml, while no meaningful changes
were observed in the control group.
In addition, this base-editing therapy has also achieved a sustained decrease in serum hepatitis B virus DNA content (3 log10 copy numbers/ml) and no rebound of viral levels has been observed
.
On the other hand, a decrease in serum viral DNA content was observed in mice in the control group when receiving therapy, but the viral DNA content also rebounded
after stopping the drug.
According to the press release, these findings show the potential of base editing therapy to avoid hepatitis B virus replication and related viral protein expression by implanting mutations, thereby achieving the therapeutic purpose of permanent inactivation of cccDNA and hepatitis B virus DNA
.
▲ Base editing therapy significantly reduces HBsAg and serum hepatitis B virus DNA levels (Source: Beam website)
"Chronic hepatitis B infection remains an important issue for
global health.
of gene and cell therapies and other high-end therapies.
WuXi Sheng is able to help customers around the world bring more innovative therapies to market early for the benefit of patients
.
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.