Maize Genomic Loci for Targeted Transgene Insertion

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current transformation methodologies for monocot plants like maize rely on random insertion of transgenes, leading to unintended gene disruption, gene silencing, and increased costs due to the need for extensive effort in identifying suitable integration locations, which hinders the effectiveness and efficiency of transgenic development.

Innovation Solution

Identification and characterization of optimal nongenic loci in the maize genome for targeted transgene insertion, using criteria such as hypomethylation, evidence of recombination, and proximity to genic regions, to facilitate site-directed insertion of exogenous sequences, thereby improving the precision and efficiency of transgenic development.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If random insertion of transgenes is used, then transformation can be achieved, but gene disruption and silencing occur

Engineering Contradiction:
Improvetransformation simplicityVSAvoidtransgene expression stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-identifying and characterizing optimal nongenic loci in the maize genome before transgene insertion. These loci are selected based on specific criteria (hypomethylation, recombination evidence, proximity to genic regions) to ensure they will support stable transgene expression. This preliminary preparation eliminates the need for random insertion and prevents gene disruption and silencing issues that would otherwise occur.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If random insertion is used, then transgenic events can be generated, but extensive screening effort is required

Engineering Contradiction:
Improvetransgenic event generationVSAvoidscreening time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent performs preliminary characterization of optimal loci attributes (hypomethylation status, recombination evidence, distance to genic regions) before transgene insertion. This pre-screening of target sites ensures that subsequent transgenic events will have high expression stability without requiring extensive post-transformation screening, thereby reducing time loss while maintaining productivity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the mechanical/screening-based approach of randomly generating transgenic events and then screening them with a targeted approach using bioinformatics criteria. By substituting computational prediction of optimal loci attributes for physical screening of transgenic events, the method maintains high productivity while dramatically reducing the time and effort required for screening.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Manufacturing precision

If targeted insertion into coding sequences is used, then precise integration is achieved, but gene function is disrupted

Engineering Contradiction:
Improveintegration precisionVSAvoidgene disruption
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by selecting specific regions of the maize genome (nongenic loci) that have particular attributes (hypomethylation, recombination evidence, proximity to but not within genic regions). These locally optimized sites provide the precise integration capability of targeted insertion while avoiding the harmful effect of gene disruption, because the insertion occurs in non-coding regions that do not interfere with gene function.

Inventive Principle:
Principle #3Local quality

Data Source

PatentEP3065540B1Optimal maize loci
Publication Date: 2021.12.15 CORTEVA AGRISCIENCE LLC
  • EP3065540B1 patent drawingFigure 1
  • EP3065540B1 patent drawingFigure 2
  • EP3065540B1 patent drawingFigure 3

AI summary

As disclosed herein, optimal native genomic loci have been identified in monocot plants, such as maize plants, that represent best sites for targeted insertion of exogenous sequences.