Progress With Developing Use of Gene Editing To Cure Chronic Infection With Hepatitis B Virus

Area of Science:

• Hepatology
• Virology
• Gene Therapy

Background:

• Chronic hepatitis B virus (HBV) infection affects 6% of the global population, posing significant health risks.
• Current treatments fail to eliminate the stable viral cccDNA, a key replication intermediate, hindering curative therapies.
• Gene editing technologies present a novel approach to permanently inactivate HBV by targeting cccDNA.

Purpose of the Study:

• To explore the potential of gene editing tools for permanent inactivation of HBV.
• To review the challenges and future directions for advancing gene editing in HBV treatment.

Main Methods:

• Utilized engineered nucleases such as zinc finger nucleases (ZFNs), TALENs, and CRISPR-Cas systems.
• Reviewed studies demonstrating inhibition of HBV replication using gene editing.
• Identified challenges including detection of cccDNA mutations and lack of suitable in vivo models.

Main Results:

• Gene editing can inhibit HBV replication by targeting cccDNA.
• Reliable detection of cccDNA mutations and in vivo efficacy in relevant models remain challenging.
• Efficient delivery to hepatocytes and minimizing off-target effects are critical for clinical translation.

Conclusions:

• Gene editing holds significant promise for a curative HBV treatment by targeting cccDNA.
• Further advancements in delivery systems, detection methods, and in vivo models are essential.
• Combination therapies, including immunotherapies, may enhance antiviral effects and clinical outcomes.