Plant eIF4E Mis-Splicing for Broad Virus Resistance

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Solution Overview

Problem

Current methods for inducing virus resistance in plants are often strain-specific and lack durability due to high mutation rates of plant viruses, necessitating new mechanisms for broad-spectrum resistance.

Innovation Solution

Development of eukaryotic translation initiation factor 4E (eIF4E) and its isoform eIF(iso)4E protein variants that are non-functional for viruses, achieved through mis-splicing processes caused by modifications in non-coding regions of the genes, specifically in splice elements, leading to aberrant splice patterns and truncated or non-functional proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mutations are introduced in the coding region (exons) of eIF4E/eIF(iso)4E genes to confer recessive resistance to potyviruses, then virus resistance is achieved, but the resistance is strain-specific and can be overcome by viral mutations

Engineering Contradiction:
Improvevirus resistanceVSAvoidbroad-spectrum resistance
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention changes the mechanism of resistance from coding region mutations to non-coding region mutations (intron splice site mutations). This parameter change in the mutation location leads to mis-splicing of the eIF4E/eIF(iso)4E transcripts, producing non-functional proteins that confer broad-spectrum resistance rather than strain-specific resistance

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a copy of the eIF4E/eIF(iso)4E gene with modified non-coding regions that produce mis-spliced transcripts. These mis-spliced transcripts generate truncated or non-functional protein variants that maintain plant function while blocking viral replication across multiple virus strains

Inventive Principle:
Principle #26Copying

2Reliability

If eIF4E or eIF(iso)4E protein function is completely eliminated to confer virus resistance, then broad-spectrum resistance is achieved, but plant viability is compromised

Engineering Contradiction:
Improvebroad-spectrum virus resistanceVSAvoidplant viability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention applies local quality by making targeted mutations only in the non-coding regions (intron splice sites) of the eIF4E/eIF(iso)4E genes, leaving the coding regions intact. This localized modification produces mis-spliced transcripts that generate non-functional proteins for viral replication while preserving enough functional protein for essential plant processes

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention uses partial action by producing a mix of functional and non-functional eIF4E/eIF(iso)4E protein variants through mis-splicing. This partial elimination of function is sufficient to block viral replication (which requires high levels of functional protein) while maintaining enough functional protein for essential plant translation processes

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentEP2585478B1Plant eukaryotic translation initiation factor 4e
Publication Date: 2023.09.20 SYNGENTA PARTICIPATIONS AG
  • EP2585478B1 patent drawingFigure 1~3
  • EP2585478B1 patent drawingFigure 4~6
  • EP2585478B1 patent drawingFigure 7

AI summary

The invention relates to plants, and in particular to virus-resistant plants, and to methods of generating such plants. The invention extends to eukaryotic translation initiation factor variants and isoforms thereof, and to nucleic acids involved in the splicing of such variant factors, and uses thereof in methods for producing plants that are resistant to viral infections.