LNA-DNA Antisense Oligonucleotide Inhibits SARS-CoV-2 Replication

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Solution Overview

Problem

Current treatments for COVID-19 caused by SARS-CoV-2 lack effective solutions for inhibiting viral replication, particularly for mutant strains, and existing antisense oligonucleotides targeting the translation initiation site (TIS-L) have shown limited efficacy.

Innovation Solution

Development of a TIS-L targeting antisense oligonucleotide with a specific nucleotide sequence (SEQ ID NO: 5 or SEQ ID NO: 7) composed of DNA and LNA nucleotides, which effectively inhibits the viral replication of both original and mutant SARS-CoV-2 strains by administering it via carriers like viral vectors, liposomes, or solid lipid nanoparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing antisense oligonucleotides targeting TIS-L are used, then viral replication inhibition is achieved, but efficacy is limited particularly against mutant strains

Engineering Contradiction:

Improveantiviral efficacyVSAvoideffectiveness against mutant strains

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical composition parameters of the oligonucleotide by incorporating LNA (locked nucleic acid) monomers alongside DNA monomers. This chemical parameter change enhances both the binding affinity and stability of the oligonucleotide to the TIS-L target sequence, resulting in improved antiviral efficacy against both wild-type and mutant SARS-CoV-2 strains while maintaining sequence-specific targeting

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses a composite oligonucleotide structure combining DNA and LNA components. This composite material approach leverages the advantages of both DNA (sequence specificity and biocompatibility) and LNA (enhanced binding affinity and nuclease resistance), achieving superior and broader antiviral activity including against mutant strains

Inventive Principle:

Principle #40Composite materials

2Reliability

If high doses of antiviral agents are administered, then viral replication inhibition is enhanced, but cytotoxicity increases

Engineering Contradiction:

Improveviral replication inhibitionVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The modified oligonucleotide with LNA incorporation achieves high antiviral efficacy at low doses due to enhanced binding affinity and stability. This parameter change in chemical composition allows achieving effective viral replication inhibition with reduced dosing, thereby minimizing cytotoxic effects on host cells

Inventive Principle:

Principle #35Parameter changes

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 oligonucleotide exhibits a high antiviral efficacy of 90% or more even at low doses, effectively inhibiting viral replication across various SARS-CoV-2 strains, including mutants, and demonstrates minimal cytotoxicity, making it suitable for COVID-19 treatment.

Implementation Method 1

an antisense oligonucleotide (ASO), which inhibits the function of TIS-L

Methodology Applied

Scientific EffectComplementary base pairing:

Implementation Method 2

TIS-L targeting antisense oligonucleotide that inhibits the viral replication of SARS-COV-2

Methodology Applied

Scientific EffectHybridization:

Data Source

PatentUS20240417733A1Tis-l targeting antiviral antisense oligonucleotide with ability to inhibit viral replication of SARS-COV-2

Publication Date: 2024.12.19 SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

AI summary

The present disclosure relates to a TIS-L targeting antisense oligonucleotide that inhibits the viral replication of SARS-COV-2 and antiviral use thereof. Since the TIS-L targeting antisense oligonucleotide according to the present disclosure has a simple structure, it is easy to mass produce, and as it exhibits antiviral efficacy of 90% or more even at low doses against the original strain and various modified strains of the virus, it can be advantageously utilized in the development of COVID-19 treatment.