Evidence map›Paper›PMID 28630470›Full record

ArticleScientific reports2017

Overcoming evolved resistance to population-suppressing homing-based gene drives.

John M Marshall, Anna Buchman, Héctor M Sánchez C, Omar S Akbari

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
11.9field-weighted citation impact, top 1% of its field
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

86 citing papers in PubMed, 178 citations in OpenAlex.

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

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 at 3 institutions in 2 countries.

John M MarshallDivisions of Biostatistics and Epidemiology, School of Public Health, University of California, Berkeley, CA, 94720, USA. john.marshall@berkeley.edu.
Anna BuchmanDepartment of Entomology, Center for Disease Vector Research, and Institute for Integrative Genome Biology, University of California, Riverside, CA, 92521, USA.
Héctor M Sánchez CBioinformatics Research Group, School of Medicine, Tecnológico de Monterrey, Estado de México, 52926, México, USA.ORCID 0000-0003-3272-4786
Omar S AkbariDepartment of Entomology, Center for Disease Vector Research, and Institute for Integrative Genome Biology, University of California, Riverside, CA, 92521, USA. omar.akbari@ucr.edu.
University of California, Riverside · USTecnológico de Monterrey · MXUniversity of California, Berkeley · US

Funding

Developing reciprocal chromosomal translocations for wild population replacement in an important vector of human disease.R21AI123937 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2017 to 2018
$427k
Synthetically engineering population control systems in vectors of human diseaseK22AI113060 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2015 to 2016
$270k
NIAID NIH HHS K22 AI113060NIAID NIH HHS R21 AI123937
6 · The paper itself

Abstract

The recent development of a CRISPR-Cas9-based homing system for the suppression of Anopheles gambiae is encouraging; however, with current designs, the slow emergence of homing-resistant alleles is expected to result in suppressed populations rapidly rebounding, as homing-resistant alleles have a significant fitness advantage over functional, population-suppressing homing alleles. To explore this concern, we develop a mathematical model to estimate tolerable rates of homing-resistant allele generation to suppress a wild population of a given size. Our results suggest that, to achieve meaningful population suppression, tolerable rates of resistance allele generation are orders of magnitude smaller than those observed for current designs for CRISPR-Cas9-based homing systems. To remedy this, we theoretically explore a homing system architecture in which guide RNAs (gRNAs) are multiplexed, increasing the effective homing rate and decreasing the effective resistant allele generation rate. Modeling results suggest that the size of the population that can be suppressed increases exponentially with the number of multiplexed gRNAs and that, with four multiplexed gRNAs, a mosquito species could potentially be suppressed on a continental scale. We also demonstrate successful proof-of-principle use of multiplexed ribozyme flanked gRNAs to induce mutations in vivo in Drosophila melanogaster - a strategy that could readily be adapted to engineer stable, homing-based drives in relevant organisms.

Indexed as

AllelesCRISPR-Cas SystemsModels, GeneticMutationAnimalsAnophelesDrosophila melanogaster

Identifiers

PMID28630470
PMCPMC5476637
OpenAlexW2952000730

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.