Dual Female-Specific Lethal Gene System for Insect Control

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Solution Overview

Problem

Existing methods for controlling insect populations, such as the Sterile Insect Technique (SIT) and temperature-sensitive-lethal (TSL) sexing strains, face challenges including high costs, labor-intensive sorting, and instability, while female-specific repressible dominant lethal genetic systems have issues with biochemical resistance and inefficient lethality timing.

Innovation Solution

A dual female-specific, repressible, dominant lethal genetic system is introduced, comprising two gene expression systems with activating transcription factors and splice control sequences, which activate promoters for dominant lethal genes, ensuring female-specific expression and repressibility, thereby improving penetrance and reducing resistance risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single female-specific repressible dominant lethal genetic system is used, then female-specific lethality is achieved, but biochemical resistance may develop and penetrance is reduced

Engineering Contradiction:

Improvelethality effectivenessVSAvoidbiochemical resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent divides the single lethal gene system into two separate dominant lethal genes (first dominant lethal gene and second dominant lethal gene), each under independent regulatory control. This segmentation ensures that even if resistance develops to one lethal pathway, the other remains effective, thereby reducing the risk of biochemical resistance and improving overall reliability of female-specific lethality.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a composite genetic system by combining two different dominant lethal genes with their respective activating transcription factors and regulatory elements into a unified transgene construct. This composite approach leverages the synergistic effect of multiple lethal pathways, enhancing penetrance and preventing resistance while maintaining female-specific expression through integrated splice control sequences.

Inventive Principle:

Principle #40Composite materials

2Reliability

If a female-specific repressible dominant lethal genetic system is used, then female-specific lethality is achieved, but the onset of lethality is delayed and penetrance is reduced

Engineering Contradiction:

Improvefemale-specific lethalityVSAvoidonset timing of lethality

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent incorporates two activating transcription factors that are expressed constitutively from early developmental stages, with their corresponding dominant lethal genes activated by female-specific splice control sequences. This preliminary arrangement ensures that the lethal effect is triggered earlier in development rather than delayed, improving both the timing and penetrance of female-specific lethality.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs a feedback mechanism where the activating transcription factors enhance the expression of their corresponding dominant lethal genes, which in turn reinforce the lethal pathway. This positive feedback loop accelerates the onset of lethality and increases penetrance by ensuring robust activation of the lethal effect once female-specific splicing occurs.

Inventive Principle:

Principle #23Feedback

3Ease of operation

If manual sorting of insects is used to separate males and females, then sex separation is achieved, but the process is labor-intensive and time-consuming

Engineering Contradiction:

Improvesex separationVSAvoidsorting time

Core Design Contradiction:

Ease of operationVSLoss of time

Solution Approach 1:

The patent replaces the mechanical manual sorting system with a genetic-based automatic separation system. By introducing a female-specific repressible dominant lethal genetic system, females are automatically eliminated during development, leaving only males in the population. This eliminates the need for labor-intensive manual sorting and significantly reduces the time required for sex separation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Productivity

If irradiation is used to render males infertile in SIT, then insect population control is achieved, but the method is not economically viable in all areas and requires similar behavior patterns to wild populations

Engineering Contradiction:

Improveinsect population control efficiencyVSAvoideconomic viability

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent changes the fundamental parameter of infertility induction from physical irradiation to genetic control. Instead of using radiation to damage male sterility, the system uses a female-specific lethal gene that naturally eliminates females during development. This genetic approach improves economic viability by eliminating the need for expensive irradiation equipment and reduces the requirement for behavior pattern matching, as the genetic mechanism works regardless of wild population characteristics.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11737436B2Gene expression system

Publication Date: 2023.08.29 OXITEC LTD

AI summary

Two or more conditional, dominant, lethal gene expression systems provide high levels of penetrance in insects. Lethality is induced at an earlier stage of development and the risk of biochemical resistance is reduced, as compared to a single insect conditional, dominant, lethal gene expression system. The invention is useful for the control of insect populations.