RTEL1 Antisense Oligonucleotides for HBV cccDNA Destabilization
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Solution Overview
Problem
Current treatments for chronic HBV infection do not effectively target cccDNA, and existing treatments for HBV do not effectively eliminate cccDNA, and existing treatments for HBV do not target cccDNA.
Innovation Solution
The use of RTEL1 inhibitors, such as oligonucleotides, specifically designed to target and destabilize cccDNA, which are capable of reducing cccDNA and pgRNA levels in HBV-infected cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments (nucleos(t)ide analogues or interferons) are used to treat chronic HBV infection, then viral replication is suppressed, but cccDNA persists and cannot be eliminated
Solution Approach 1:
The invention extracts and targets the specific function of RTEL1 helicase that maintains cccDNA stability. By using siRNA to specifically knock down RTEL1 expression, the patent removes the protective function RTEL1 provides to cccDNA, allowing cccDNA to be eliminated without affecting other viral replication processes suppressed by conventional treatments
Solution Approach 2:
The invention introduces RTEL1 siRNA as an intermediary molecule that mediates between the treatment goal (cccDNA elimination) and the biological system. The siRNA acts as a mediator that specifically targets RTEL1 mRNA, reducing RTEL1 protein levels and thereby destabilizing cccDNA without directly interacting with cccDNA itself
2Object-generated harmful factors
If RTEL1 is inhibited to destabilize cccDNA, then cccDNA levels are reduced, but potential off-target effects on telomere maintenance and DNA repair may occur
Solution Approach 1:
The invention applies partial action by using transient siRNA treatment that temporarily reduces RTEL1 levels sufficient to destabilize cccDNA without completely eliminating RTEL1 function. This partial knockdown achieves cccDNA elimination while maintaining enough RTEL1 activity to preserve telomere maintenance and DNA repair functions
Solution Approach 2:
The invention changes the parameter of RTEL1 expression levels from normal physiological levels to a reduced but non-zero level through siRNA-mediated gene silencing. This parameter change is sufficient to disrupt cccDNA stability while maintaining genomic and telomeric stability
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 RTEL1 inhibitors effectively reduce cccDNA and pgRNA levels, providing a potential cure for chronic HBV infection.
Implementation Method 1
An oligonucleotide as defined above may hybridize to a target nucleic acid
Implementation Method 2
The oligonucleotide may be capable of recruiting RNase H when forming a hybridization duplex with the target nucleic acid
Data Source
AI summary
The present invention relates to a RTEL1 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of RTEL1 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to antisense oligonucleotides which are complementary to RTEL1 and capable of reducing a RTEL1 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment and/or prevention of a HBV infection.