Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives.

@article{Xu2020ActiveGN,
  title={Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives.},
  author={Xiang-Ru Shannon Xu and Emily A. Bulger and Valentino Matteo Gantz and Carissa F. Klanseck and Stephanie R Heimler and Ankush Auradkar and Jared B. Bennett and Lauren Ashley Miller and Sarah Leahy and Sara Sanz Juste and Anna B. Buchman and Omar S. Akbari and John M. Marshall and Ethan Bier},
  journal={Molecular cell},
  year={2020}
}

Figures from this paper

Genetic conversion of a split-drive into a full-drive element

TLDR
Experimental proof-of-principle is provided for a convertible system inserted at the spo11 locus, which is recoded to restore gene function and initially drives with slower kinetics than the unlinked sGD element, but eventually reaches a similar level of final introgression.

Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

TLDR
A method for overcoming resistance alleles “double-tap,” that encodes additional gRNAs in the gene drive that target the most common generated resistance allele, allowing a second opportunity at gene-drive conversion.

A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression

TLDR
Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.

Gene drives gaining speed

  • E. Bier
  • Biology
    Nature reviews. Genetics
  • 2021
TLDR
How several impactful technical advancements, particularly involving CRISPR-based methods, are providing a diverse toolkit of gene-drive systems for the control of populations such as insect vectors of disease is discussed.

Active genetics comes alive

  • V. GantzE. Bier
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2022
TLDR
The substantial advances that have been made on all of these fronts are summarized and the next phase of this rapidly expanding and impactful field is looked forward to.

A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles

TLDR
A homing suppression drive in Drosophila melanogaster is constructed that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene and reaches a moderate equilibrium frequency in cage populations without apparent formation of resistance allele.

Modeling homing suppression gene drive in haplodiploid organisms

TLDR
Examining models of continuous space where organisms move over a landscape, it is found that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due to their ability to spread further before inducing strong suppression.

The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives

TLDR
The history of homing gene drive development is charted, highlighting the emergence of challenges such as unintended repair outcomes, “leaky” expression, and parental deposition and the progress made in developing strategies to increase the efficiency of hning endonuclease gene drives and mitigate or prevent unintended outcomes.

Genetic Approaches for Controlling CRISPR-based Autonomous Homing Gene Drives

TLDR
There is an imminent need for countermeasures or technologies capable of exerting precise spatiotemporal control of gene drives, if their transformative potential is ever to be fully realized.

Experimental demonstration of tethered gene drive systems for confined population modification or suppression

TLDR
The engineering of a tethered drive system in Drosophila is demonstrated, using a regionally confined CRISPR Toxin-Antidote Recessive Embryo (TARE) drive to support modification and suppression homing drives.

References

SHOWING 1-10 OF 51 REFERENCES

A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus

TLDR
This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with ~ 100-fold greater efficiency than control CRISPR-based methods, suggesting an amplifying positive feedback loop due to increasing gRNA dosage.

Evaluating strategies for reversing CRISPR-Cas9 gene drives

TLDR
A discrete time model for population genetics of a drive and proposed genetic countermeasures is developed and predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics.

Efficient allelic-drive in Drosophila

TLDR
An allelic-drive for selective inheritance of a desired allele, enhanced by lethal mosaicism and a trans-generational drive process the authors refer to as “shadow-drive”, has broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.

Cas9-triggered chain ablation of cas9 as a gene drive brake

TLDR
A potential Cas9-based gene drive 'brake' that remains inert in a wild-type genome but is activated by Cas9 to both cleave the genomic cas9 sequence and to convert an incoming cas9 allele into a brake means that the propagation of the brake is favored in a cas9-carrying population.

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

TLDR
Two CRISPR gene drive constructs based on the nanos and vasa promoters were developed that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster.

Site-specific selfish genes as tools for the control and genetic engineering of natural populations

  • A. Burt
  • Biology
    Proceedings of the Royal Society of London. Series B: Biological Sciences
  • 2003
TLDR
The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Super-Mendelian inheritance mediated by CRISPR/Cas9 in the female mouse germline

TLDR
The results demonstrate the feasibility of CRISPR–Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.

CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations

TLDR
It is shown that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive, and concludes that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.

A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

TLDR
A trans-complementing split-gene drive that requires inheritance of separate transgenes to assemble a fully functional drive and demonstrates its ability to promote super-Mendelian inheritance of the separate trans genes.

Safeguarding CRISPR-Cas9 gene drives in yeast

TLDR
The efficacy of CRISPR-Cas9 gene drive systems in wild and laboratory strains of the yeast Saccharomyces cerevisiae is reported and concerns surrounding accidental genome editing are addressed by developing and validating methods of molecular confinement that minimize the risk of unwanted genome editing.
...