AAV-Cas13d Vectors Targeting Conserved SARS-CoV-2 RNA

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Solution Overview

Problem

Current therapies and vaccines for SARS-CoV-2 are inadequate, and there is an urgent need for effective treatments against coronavirus infections, particularly for SARS-CoV, MERS-CoV, and SARS-CoV-2, which are highly infectious and cause severe respiratory diseases.

Innovation Solution

The use of AAV vectors carrying Cas13d and guide RNAs specifically designed to target conserved regions of the SARS-CoV-2 genome, facilitating the Cas13d protein's cleavage of viral RNA, thereby inhibiting viral replication and spread.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapies and vaccines are used for SARS-CoV-2, then treatment is provided, but they are inadequate and fail to effectively treat coronavirus infections

Engineering Contradiction:

Improveefficacy of treatmentVSAvoideffectiveness against current and future variants

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent designs guide RNAs that target highly conserved regions of the coronavirus genome that are shared across SARS-CoV-2, SARS-CoV, and MERS-CoV. This universal targeting approach allows a single therapeutic platform to be effective against multiple coronavirus variants and species, addressing the need for both current and future variant effectiveness

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If Cas13d and guide RNAs are used to target viral RNA, then viral replication is inhibited, but delivery into infected cells must be achieved

Engineering Contradiction:

Improveviral cleavage efficacyVSAvoiddelivery system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs AAV (adeno-associated virus) vectors as intermediary delivery vehicles to transport the Cas13d protein and guide RNA into infected cells. The AAV vector serves as a safe and efficient mediator that protects the therapeutic components during delivery while enabling their entry into target cells, thus simplifying the overall delivery system

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The therapeutic approach is designed to be administered early in the infection course to prevent viral replication before it progresses. By acting preliminarily, the treatment can inhibit viral spread more effectively, reducing the burden on the delivery system and improving overall efficacy

Inventive Principle:

Principle #10Preliminary action

3Adaptability or versatility

If guide RNAs target conserved regions of coronavirus genome, then broad coverage against family members is achieved, but specificity to particular variants must be maintained

Engineering Contradiction:

Improvecoverage of coronavirus familyVSAvoidtargeting specificity

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing guide RNAs that specifically target highly conserved regions within the coronavirus genome that are essential for viral function. By focusing on these specific local regions that are both conserved and functionally critical, the treatment achieves broad coverage while maintaining the precision needed to effectively inhibit viral replication across variants

Inventive Principle:

Principle #3Local quality

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

This approach effectively targets and degrades SARS-CoV-2 RNA, offering a promising therapeutic strategy for treating coronavirus infections by enhancing specificity and efficacy while minimizing side effects, potentially providing immediate protection against current and future coronavirus variants.

Implementation Method 1

Cas13 targeting and cleavage of single-stranded RNA to target and cleave the genome of a single stranded RNA virus of the Coronaviridae family

Methodology Applied

Scientific EffectCRISPR/Cas13d RNA targeting and cleavage: Enzyme

Implementation Method 2

AAV vectors comprising a Cas13d as well as a guide RNA expression cassette are used as a vehicle for the transport of Cas13d into a cell infected with a virus

Methodology Applied

Scientific EffectViral vector transduction:

Data Source

PatentEP4034661B1All-in-one AAV vectors for treating coronavirus-induced diseases

Publication Date: 2023.09.06 GEORG AUGUST UNIVERSITAT GOTTINGEN STIFTUNG OFFENLICHEN RECHTS

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AI summary

The present invention relates to a novel approach for treating coronavirus infections, particularly infections caused by MERS-CoV, SARS-CoV and SARS-CoV-2 variants. Based on effectively targeting and cleaving single stranded RNA viruses, the present invention provides CaslBd guide RNAs, to guide the CaslBd protein to a target site in the genome of humanized Coronaviridae that is conserved between MERS-CoV, SARS-CoV and SARS-CoV-2. The disclosed invention further provides an AAV vector comprising such a CaslBd guide RNA expression cassette as well as a CaslBd for treating coronavirus infections, especially COVID- 19 infections.