HBV Epigenetic Editing for cccDNA Silencing Without DNA Cleavage

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Solution Overview

Problem

Current treatments for hepatitis B virus (HBV) infection, such as nucleoside analogs and IFN, fail to achieve a functional cure due to the persistence of covalently closed circular DNA (cccDNA) and integrated DNA, which continue to serve as templates for viral replication and protein expression, necessitating long-term medication and risking rebound upon cessation.

Innovation Solution

An epigenetic editing tool comprising a fusion molecule with a DNA binding protein and a gene expression modulator, guided by a single guide RNA (sgRNA) targeting specific regulatory regions of the HBV genome, introduces inhibitory modifications to silence cccDNA and integrated DNA, reducing viral replication and protein expression without causing DNA cleavage or activating DNA repair mechanisms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments (nucleoside analogs and IFN) are used to inhibit HBV replication, then viral replication is suppressed, but cccDNA and integrated DNA persist and require long-term medication

Engineering Contradiction:

Improveinhibition of viral replicationVSAvoidpersistence of cccDNA and integrated DNA

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent extracts and targets the specific problem of cccDNA persistence by designing epigenetic editing tools that specifically recognize and modify cccDNA structures, separating the treatment of replicating virus from the elimination of persistent cccDNA reservoirs

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the treatment parameter from direct viral replication inhibition to epigenetic modification of cccDNA, using DNA methyltransferases and histone modifiers to alter the epigenetic state of cccDNA, converting it from a transcriptionally active to a silenced state

Inventive Principle:

Principle #35Parameter changes

2Reliability

If DNA cleavage is used to eliminate cccDNA, then viral templates are destroyed, but DNA repair mechanisms are activated and immunogenic truncated proteins may be produced

Engineering Contradiction:

Improveelimination of viral templatesVSAvoidDNA repair activation and immunogenic proteins

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the potential harm of DNA cleavage into benefit by using the natural DNA repair machinery and chromatin remodeling processes to achieve silencing of cccDNA without causing double-strand breaks, thereby eliminating the harmful effects while maintaining the therapeutic goal

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces epigenetic modifiers as intermediaries between the therapeutic goal and the cccDNA target, using DNA methyltransferases and histone modifiers that can silence gene expression without directly cleaving DNA, thus avoiding the activation of harmful DNA repair mechanisms

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If epigenetic editing tools are developed to silence HBV, then cccDNA can be targeted, but the technology is still in early stage and faces unknown limitations

Engineering Contradiction:

Improvetargeting capability of cccDNAVSAvoidmaturity of epigenetic editing technology

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent designs epigenetic editing tools with universal applicability by using modular components that can target multiple HBV genes and regulatory elements simultaneously, allowing a single platform to address various aspects of HBV persistence through epigenetic silencing

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent segments the complex problem of HBV elimination into manageable components by designing separate epigenetic editing modules that can be independently optimized for different targets (cccDNA, integrated DNA, specific viral genes), allowing systematic development and validation of each component

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The tool effectively reduces HBV replication and protein expression, potentially leading to a sustainable cure by altering the chromatin structure and transcriptional regulation of the HBV genome, thereby treating hepatitis B infection.

Implementation Method 1

the sgRNA is complementary to a target DNA sequence in the vicinity of a hepatitis B virus (HBV) gene and/or within a HBV gene regulatory element

Methodology Applied

Scientific EffectComplementary base pairing:

Implementation Method 2

introduces inhibitory modifications to silence cccDNA and integrated DNA, reducing viral replication and protein expression

Methodology Applied

Scientific EffectEpigenetic modification:

Data Source

PatentEP4729075A1Epigenetic editing tool for targeting hepatitis b virus gene

Publication Date: 2026.04.22 EPIGENIC THERAPEUTICS PTE LTD

Figure 1A~1B
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Figure 2B

AI summary

The present application relates to the field of biomedicine, and provides an epigenetic editing tool for targeting a hepatitis B virus gene and a use thereof.