Evidence map›Paper›PMID 28727785›Full record

ArticlePLoS genetics2017

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

Jackson Champer, Riona Reeves, Suh Yeon Oh, Chen Liu, Jingxian Liu, Andrew G Clark, Philipp W Messer

Abstract read
In one paragraph

Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.

0numbers the graph read from it
0cells of the map it votes in
164citing 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

164 citing papers in PubMed.

  1. Cost-Effectiveness of the Strategies to Reduce the Incidence of Dengue in Colima, México.International journal of environmental research and public health · 2017
    Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

104 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Jackson ChamperDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0002-3814-3774
Riona ReevesDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0003-0236-4046
Suh Yeon OhDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0002-6908-9336
Chen LiuDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.
Jingxian LiuDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0002-2172-3297
Andrew G ClarkDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0001-7159-8511
Philipp W MesserDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, United States of America.ORCID 0000-0001-8453-9377

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.

Indexed as

Genetics, PopulationAllelesAnimalsAnimals, Genetically ModifiedCRISPR-Cas SystemsDisease ResistanceDrosophila melanogasterEmbryonic DevelopmentFertilizationGene ConversionGerm CellsMutationTransgenes

Identifiers

PMID28727785
PMCPMC5518997

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.