Evidence map›Paper›PMID 36656895›Full record

ArticlePLoS pathogens2023

CRISPR mediated transactivation in the human disease vector Aedes aegypti.

Michelle Bui, Elena Dalla Benetta, Yuemei Dong, Yunchong Zhao, Ting Yang, Ming Li, Igor A Antoshechkin, Anna Buchman, Vanessa Bottino-Rojas, Anthony A James and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

13 authors at 4 institutions in 1 country.

Michelle BuiDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Elena Dalla BenettaDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Yuemei DongW. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Yunchong ZhaoDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Ting YangDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Ming LiDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Igor A AntoshechkinDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
Anna BuchmanDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
Vanessa Bottino-RojasDepartment of Microbiology & Molecular Genetics, University of California Irvine, Irvine, California, United States of America.
Anthony A JamesDepartment of Microbiology & Molecular Genetics, University of California Irvine, Irvine, California, United States of America.
Michael W PerryDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.
George DimopoulosW. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Omar S AkbariDepartment of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.ORCID 0000-0002-6853-9884
University of California San Diego · USJohns Hopkins University · USUniversity of California, Irvine · USCalifornia Institute of Technology · US

Funding

Aedes antiviral RNAi pathwayR01AI141532 · NIAID · JOHNS HOPKINS UNIVERSITY · PI George Dimopoulos, KEVIN M MYLES · 2019 to 2026
$4.6M
Development of synthetic viral circuitry to regulate viruses in mosquito disease vectorsDP2AI152071 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2019 to 2019
$2.4M
Precision guided SIT for the control of vector-borne diseaseR01AI151004 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2020 to 2024
$2.3M
Transcriptome engineering technologies for the development of antiviral effectors in mosquitoesR21AI149161 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2020 to 2021
$434k
NIAID NIH HHS DP2 AI152071NIAID NIH HHS R01 AI141532NIAID NIH HHS R01 AI151004NIAID NIH HHS R21 AI149161
6 · The paper itself

Abstract

As a major insect vector of multiple arboviruses, Aedes aegypti poses a significant global health and economic burden. A number of genetic engineering tools have been exploited to understand its biology with the goal of reducing its impact. For example, current tools have focused on knocking-down RNA transcripts, inducing loss-of-function mutations, or expressing exogenous DNA. However, methods for transactivating endogenous genes have not been developed. To fill this void, here we developed a CRISPR activation (CRISPRa) system in Ae. aegypti to transactivate target gene expression. Gene expression is activated through pairing a catalytically-inactive ('dead') Cas9 (dCas9) with a highly-active tripartite activator, VP64-p65-Rta (VPR) and synthetic guide RNA (sgRNA) complementary to a user defined target-gene promoter region. As a proof of concept, we demonstrate that engineered Ae. aegypti mosquitoes harboring a binary CRISPRa system can be used to effectively overexpress two developmental genes, even-skipped (eve) and hedgehog (hh), resulting in observable morphological phenotypes. We also used this system to overexpress the positive transcriptional regulator of the Toll immune pathway known as AaRel1, which resulted in a significant suppression of dengue virus serotype 2 (DENV2) titers in the mosquito. This system provides a versatile tool for research pathways not previously possible in Ae. aegypti, such as programmed overexpression of endogenous genes, and may aid in gene characterization studies and the development of innovative vector control tools.

Indexed as

AedesAnimalsCRISPR-Cas SystemsHedgehog ProteinsHumansMosquito VectorsRNATranscriptional ActivationHedgehog ProteinsRNA

Identifiers

PMID36656895
PMCPMC9888728
OpenAlexW4317437826

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.