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Updated: Sep 18, 2025

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target

Published on: May 10, 2022

Lipid Nanoparticle-Encapsulated TALEN-Encoding mRNA Inactivates Hepatitis B Virus Replication in Cultured Cells and

Tiffany Smith¹, Prashika Singh¹, Ridhwaanah Bhana¹

¹Wits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.

|August 28, 2025

Summary

New gene-editing therapy using transcription activator-like effector nucleases (TALENs) mRNA shows promise for permanently disabling hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) reservoirs, offering a potential cure for chronic HBV infection.

Keywords:

HBV HBsAg LNP TALEN mRNA cccDNA core

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Area of Science:

Hepatology
Gene Therapy
Virology

Background:

Chronic hepatitis B virus (HBV) infection causes over 1 million deaths annually.
Current treatments inhibit HBV replication but rarely eliminate cccDNA, maintaining chronic infection.
Novel strategies targeting cccDNA are crucial for a permanent HBV cure.

Purpose of the Study:

To investigate the therapeutic potential of transcription activator-like effector nucleases (TALENs) mRNA for permanent HBV inactivation.
To develop a gene-editing strategy targeting HBV cccDNA using TALENs.

Main Methods:

TALEN-encoding mRNA targeting HBV core and surface genes was synthesized.
TALEN mRNA was delivered via lipid nanoparticles in a HBV transgenic murine model.
Cell culture and animal models were used to assess HBsAg reduction, viral particle levels, and HBV DNA mutation rates.

Main Results:

TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in cell culture.
A single dose of TALEN mRNA in mice lowered HBsAg by 63% and reduced viral particle equivalents by over 99%.
In vivo HBV DNA mutation rates of approximately 15-16% were observed for Core and Surface TALENs, with no toxicity.

Conclusions:

TALEN-encoding mRNA demonstrates significant potential for permanently inactivating HBV replication.
This study provides the first evidence for TALEN mRNA as a therapeutic strategy against persistent HBV cccDNA.
TALEN mRNA therapy offers a promising new avenue for a functional cure of chronic hepatitis B.