Evidence map›Paper›PMID 36121880›Full record

ArticlePLoS genetics2022

Daisy-chain gene drives: The role of low cut-rate, resistance mutations, and maternal deposition.

Sebald A N Verkuijl, Michelle A E Anderson, Luke Alphey, Michael B Bonsall

Abstract read
In one paragraph

Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Sebald A N VerkuijlDepartment of Biology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-6771-0280
Michelle A E AndersonArthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom.ORCID 0000-0003-1510-2942
Luke AlpheyArthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom.
Michael B BonsallDepartment of Biology, University of Oxford, Oxford, United Kingdom.

Funding

Biotechnology and Biological Sciences Research Council BB/H01814X/1Biotechnology and Biological Sciences Research Council BB/L00948X/1Biotechnology and Biological Sciences Research Council BB/M011224/1Biotechnology and Biological Sciences Research Council BBS/E/I/00007033Biotechnology and Biological Sciences Research Council BBS/E/I/00007038Biotechnology and Biological Sciences Research Council BBS/E/I/00007039Biotechnology and Biological Sciences Research Council BB/V008110/1
6 · The paper itself

Abstract

The introgression of genetic traits through gene drive may serve as a powerful and widely applicable method of biological control. However, for many applications, a self-perpetuating gene drive that can spread beyond the specific target population may be undesirable and preclude use. Daisy-chain gene drives have been proposed as a means of tuning the invasiveness of a gene drive, allowing it to spread efficiently into the target population, but be self-limiting beyond that. Daisy-chain gene drives are made up of multiple independent drive elements, where each element, except one, biases the inheritance of another, forming a chain. Under ideal inheritance biasing conditions, the released drive elements remain linked in the same configuration, generating copies of most of their elements except for the last remaining link in the chain. Through mathematical modelling of populations connected by migration, we have evaluated the effect of resistance alleles, different fitness costs, reduction in the cut-rate, and maternal deposition on two alternative daisy-chain gene drive designs. We find that the self-limiting nature of daisy-chain gene drives makes their spread highly dependent on the efficiency and fidelity of the inheritance biasing mechanism. In particular, reductions in the cut-rate and the formation of non-lethal resistance alleles can cause drive elements to lose their linked configuration. This severely reduces the invasiveness of the drives and allows for phantom cutting, where an upstream drive element cuts a downstream target locus despite the corresponding drive element being absent, creating and biasing the inheritance of additional resistance alleles. This phantom cutting can be mitigated by an alternative indirect daisy-chain design. We further find that while dominant fitness costs and maternal deposition reduce daisy-chain invasiveness, if overcome with an increased release frequency, they can reduce the spread of the drive into a neighbouring population.

Indexed as

Gene Drive TechnologyAllelesCRISPR-Cas SystemsMutation

Identifiers

PMID36121880
PMCPMC9521892

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.