Schmallenberg Virus Reverse Genetics via Segmented cDNA Constructs

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Solution Overview

Problem

The lack of available vaccines and effective reverse genetic systems for the Schmallenberg virus (SBV) hinders the understanding of its diseases, vaccine development, and diagnostic tools, due to sparse genome sequence information and challenging reverse genetic systems for Orthobunyaviruses.

Innovation Solution

Development of nucleic acid molecules comprising complete genomic sequences of SBV genome segments, specifically cDNA molecules with high sequence identity, capable of producing infectious SBV when transfected into cells, using T7 RNA polymerase and transgenic cells, to establish a reverse genetics system for studying SBV and developing vaccines and diagnostics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If complete genome sequences of SBV are developed and stored, then the ability to produce infectious SBV and conduct research is improved, but the complexity of managing and maintaining these biological materials increases

Engineering Contradiction:
Improvereliability of reverse genetics systemVSAvoidcomplexity of genome sequence management
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the SBV genome into three separate cDNA constructs (S, M, and L segments), each stored and maintained independently. This segmentation allows for easier management, storage, and manipulation of the viral genome sequences while maintaining the ability to reconstruct infectious virus when needed, thereby improving reliability without excessive complexity.

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If reverse genetic systems are established for SBV, then vaccine development and disease understanding are improved, but the time and resources required for system development increase

Engineering Contradiction:
Improveversatility for vaccine developmentVSAvoidtime for system establishment
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent performs preliminary actions by developing and storing the complete cDNA sequences of all three SBV genome segments (S, M, and L) in advance. This preliminary preparation of the genetic material allows for rapid establishment of reverse genetics systems and accelerates subsequent vaccine development and research activities, reducing the time required when actual applications are needed.

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If complete genome sequences are made available, then diagnostic and vaccine development capabilities are improved, but the risk of misuse or accidental release increases

Engineering Contradiction:
Improveease of diagnostic tool productionVSAvoidrisk of virus release
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent uses cDNA sequences as an intermediary form between the viral RNA genome and infectious virus production. The cDNA constructs serve as a safe, non-infectious intermediate that can be stored, transported, and manipulated without the hazards of live virus. This intermediary step enables easy production of diagnostics and vaccines while minimizing the risk of accidental virus release, as the cDNA itself is not infectious.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Enables the production of infectious SBV for studying disease mechanisms and developing vaccines and diagnostics, facilitating the generation of recombinant SBV and defined mutants for investigating virus-host interactions and pathogenesis.

Implementation Method 1

capable of producing infectious SBV when transfected into cells, using T7 RNA polymerase

Methodology Applied
Scientific EffectTranscription:

Implementation Method 2

when transfected into cells, using T7 RNA polymerase and transgenic cells, to establish a reverse genetics system

Methodology Applied
Scientific EffectTranslation:

Data Source

PatentEP2855512B1Genomic sequences of schmallenberg virus and uses thereof
Publication Date: 2018.02.28 BOEHRINGER INGELHEIM VETMEDICA GMBH
  • EP2855512B1 patent drawingFigure 1A
  • EP2855512B1 patent drawingFigure 1B
  • EP2855512B1 patent drawingFigure 1C

AI summary

The present invention belongs to the field of animal health and relates to a nucleic acid sequence which comprises the complete genome of an infectious Schmallenberg virus (SBV) useful for studying viremia and diseases caused by SBV in ruminants, and in the development of vaccines, therapeutics and diagnostics for the prophylaxis, treatment and diagnosis of viremia and diseases caused by SBV.