Daisyfield Gene Drives for Localized CRISPR Activity

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current gene drive systems face challenges in efficiently and safely introducing desired traits into wild populations of organisms, particularly in ensuring controlled and localized spread without risking global dissemination.

Innovation Solution

The development of daisy chain and daisyfield gene drive systems, which utilize CRISPR-based components arranged in interdependent chains to confine gene drive activity locally, allowing for controlled release and spread of genetic modifications within specific populations while preventing global dissemination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If gene drive elements are released into wild populations, then desired traits can be introduced efficiently, but uncontrolled global dissemination and safety risks increase

Engineering Contradiction:
Improveefficiency of trait introductionVSAvoidsafety and control of gene drive spread
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The gene drive system is divided into multiple independent loci (at least two repeated regions in the genome) that can be independently manipulated. Each locus contains gene drive elements that target specific repeated genomic sequences, allowing the population to be edited at multiple locations simultaneously while maintaining control over the spread dynamics at each location.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The gene drive elements are designed to target specific repeated genomic sequences (such as ribosomal RNA gene clusters) that are locally concentrated in the genome. By directing the nuclease to cut only at these specific repeated regions, the system achieves localized genetic modification without affecting the entire genome, and the spread can be confined to specific population contexts.

Inventive Principle:
Principle #3Local quality

2Productivity

If multiple copies of gene drive elements are inserted into the genome, then trait introduction efficiency increases, but complexity of genome manipulation increases

Engineering Contradiction:
Improveefficiency of gene drive spreadVSAvoidcomplexity of genome manipulation
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The gene drive elements are designed to recognize and target repeated genomic sequences that occur multiple times throughout the genome (such as ribosomal RNA gene clusters). A single gene drive element can therefore target multiple identical or similar sequences across different chromosomal locations, achieving multi-locus editing with a single designed component rather than requiring separate elements for each target site.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system utilizes the natural repetition of genomic sequences (such as multiple copies of ribosomal RNA genes) to amplify the effect of the gene drive. By targeting these naturally occurring repeated sequences, the system leverages the existing genomic architecture to achieve widespread trait introduction without requiring artificial duplication of the entire gene drive construct at multiple locations.

Inventive Principle:
Principle #26Copying

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

These systems enable controlled, localized gene drive activity, ensuring that genetic modifications are confined to target populations, minimizing the risk of global spread and allowing for precise manipulation of genetic traits within ecosystems.

Implementation Method 1

inducing homologous recombination of the preselected DNA sequence with the predetermined natural sequence

Methodology Applied
Scientific EffectHomologous recombination:

Implementation Method 2

nuclease-mediated cutting and repair by homologous recombination

Methodology Applied
Scientific EffectNuclease-mediated cutting:

Implementation Method 3

repair by homologous recombination

Methodology Applied
Scientific EffectHomologous recombination:

Data Source

PatentUS20190241879A1Methods and compounds for gene insertion into repeated chromosome regions for multi-locus assortment and daisyfield drives
Publication Date: 2019.08.08 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US20190241879A1 patent drawing
  • US20190241879A1 patent drawing
  • US20190241879A1 patent drawing

AI summary

The invention relates, in part, to methods to design and construct gene drives such as daisy chain gene drives, suppression gene drives, and other types of gene drives that may be included in cell lines and organisms.