CRISPR Epigenetic Repression of HBV Genes Without DNA Disruption

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Solution Overview

Problem

Current treatments for Hepatitis B infection, such as nucleoside analogs, PEGylated interferon, and siRNA, face challenges in efficacy and stability, necessitating new methods to effectively suppress Hepatitis B viral replication and expression.

Innovation Solution

An epigenetic-modifying DNA-targeting system using CRISPR-Cas/guide RNA (gRNA) systems to repress Hepatitis B viral gene transcription by targeting specific sites in the HBV DNA sequence with fusion proteins containing a DNA-binding domain and transcriptional repressor effector domains, potentially involving multiple modules to target multiple sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current standard treatments (nucleoside analogs, PEGylated interferon, siRNA) are used to suppress viral DNA transcription, then Hepatitis B viral replication can be suppressed, but efficacy and stability face challenges

Engineering Contradiction:

Improveefficacy and stability of viral suppressionVSAvoidlimitations of current treatment effectiveness

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent replaces conventional chemical and pharmacological treatment mechanisms with a CRISPR-Cas9 based genetic targeting system. The fusion protein combines DNA-binding domain (Cas9) with transcriptional repressor effector domains to directly target and repress HBV gene transcription through epigenetic modification, achieving more reliable and stable viral suppression compared to traditional nucleoside analogs and interferon therapies

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs epigenetic modification as a mechanism to change the transcriptional state of HBV genes without altering the viral DNA sequence itself. By introducing fusion proteins that modify chromatin structure and recruit transcriptional repressors, the system achieves sustained viral gene repression through changes in epigenetic parameters rather than relying on conventional antiviral mechanisms

Inventive Principle:

Principle #35Parameter changes

2Productivity

If DNA-targeting systems are used to repress HBV gene transcription, then viral replication and protein levels are reduced, but genetic disruption may be introduced

Engineering Contradiction:

Improveviral replication reductionVSAvoidgenetic disruption

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the nuclease activity from the CRISPR-Cas9 system by using a catalytically inactive Cas9 variant (dCas9). This allows the system to bind to and target HBV DNA sequences without introducing genetic disruptions or DNA breaks, while still achieving transcriptional repression through the fusion of repressor effector domains

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of CRISPR-Cas9 induced DNA breaks into a beneficial epigenetic modification system. By using dCas9 fused with transcriptional repressors, the system achieves viral gene silencing through chromatin modification rather than DNA disruption, transforming a potentially harmful mechanism into a safe and effective therapeutic approach

Inventive Principle:

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

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 system effectively reduces HBV replication and protein levels without introducing genetic disruption, offering a stable and efficient alternative to existing treatments.

Implementation Method 1

a CRISPR-Cas/guide RNA (gRNA) system, wherein the gRNA binds a target site in a Hepatitis B viral DNA sequence

Methodology Applied

Scientific EffectBase pairing:

Data Source

PatentUS20260069716A1Compositions, systems, and methods for regulation of hepatitis b virus through targeted gene repression

Publication Date: 2026.03.12 TUNE THERAPEUTICS INC

AI summary

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and/or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.