Two-Vector Gene Drive for Reversible Population Replacement

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Solution Overview

Problem

Existing gene drive mechanisms are species-specific, challenging to implement, and lack robustness, particularly in achieving high threshold population replacement and reversibility, especially in organisms other than Drosophila.

Innovation Solution

A two-vector system comprising a first vector with a DNA sequence modifying enzyme and a second vector with a rescue transgene, configured to modify essential genes and provide rescue functions, allowing for rapid and reversible modification of populations by altering essential gene sequences and introducing cargo sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing gene drive mechanisms are used, then population replacement can be achieved, but the mechanisms are species-specific and lack robustness

Engineering Contradiction:

Improverobustness of gene driveVSAvoidspecies-specific limitation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs CRISPR-Cas9 technology, a universal gene editing platform that can be applied across multiple species, replacing species-specific gene drive mechanisms. The system uses programmable guide RNAs that can be designed to target any essential gene in any organism, making the gene drive approach universally applicable while maintaining high reliability through the precision of CRISPR-mediated gene modification.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If high threshold population replacement is achieved, then wild-type organisms are replaced, but reversibility becomes difficult

Engineering Contradiction:

Improvepopulation replacement efficiencyVSAvoidreversibility of modification

Core Design Contradiction:

ProductivityVSEase of repair

Solution Approach 1:

The patent utilizes reversible gene editing approaches where the modification parameters can be adjusted. By using CRISPR-Cas9 to create specific, controllable modifications rather than irreversible disruptions, the system allows for population replacement while maintaining the possibility of reversal through subsequent editing events or introduction of resistance alleles, thus balancing productivity with ease of repair.

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If DNA sequence modifying enzymes are used to modify essential genes, then population modification is achieved, but implementation becomes challenging

Engineering Contradiction:

Improvepopulation modification capabilityVSAvoidimplementation difficulty

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent replaces complex, difficult-to-implement gene drive mechanisms with the more manageable CRISPR-Cas9 system. This substitution uses RNA-guided DNA cleavage followed by homology-directed repair, a more controllable and easier to implement approach that maintains high adaptability for population modification across different species while reducing implementation challenges.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 rapid and high-frequency replacement of wild-type organisms with altered organisms, achieving population modification and potential reversibility, applicable to diverse species and scenarios.

Implementation Method 1

the nuclease cleaves and generates one or more double strand breaks in the endogenous copy of the essential gene; the one or more double strand breaks are repaired to create an altered sequence of the essential gene

Methodology Applied

Scientific EffectDouble strand break repair: