Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single-generation crosses and modeling Article Swipe
William Reid
,
Adeline E. Williams
,
Irma Sánchez-Vargas
,
Jing‐Yi Lin
,
Rucsanda Juncu
,
Ken E. Olson
,
Alexander W. E. Franz
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1093/g3journal/jkac280
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1093/g3journal/jkac280
The yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika viruses. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive systems. Critical to the design of a single-locus autonomous gene drive is that the selected genomic locus is amenable to both gene drive and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target 2 intergenic genomic loci, which had previously shown to be highly permissive for antiviral effector gene expression, and we further investigated the use of 3 promoters (nanos, β2-tubulin, or zpg) for Cas9 expression. We then quantified the accrual of insertions or deletions (indels) after single-generation crossings, measured maternal effects, and assessed fitness costs associated with various transgenic lines to model the rate of gene drive fixation. Overall, MGDrivE modeling suggested that when an autonomous gene drive is placed into an intergenic locus, the gene drive system will eventually be blocked by the accrual of gene drive blocking resistance alleles and ultimately be lost in the population. Moreover, while genomic locus and promoter selection were critically important for the initial establishment of the autonomous gene drive, it was the fitness of the gene drive line that most strongly influenced the persistence of the gene drive in the simulated population. As such, we propose that when autonomous CRISPR/Cas9-based gene drive systems are anchored in an intergenic locus, they temporarily result in a strong population replacement effect, but as gene drive-blocking indels accrue, the gene drive becomes exhausted due to the fixation of CRISPR resistance alleles.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/g3journal/jkac280
- https://academic.oup.com/g3journal/article-pdf/12/12/jkac280/47467940/jkac280.pdf
- OA Status
- gold
- Cited By
- 32
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4306642944
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4306642944Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/g3journal/jkac280Digital Object Identifier
- Title
-
Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single-generation crosses and modelingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-17Full publication date if available
- Authors
-
William Reid, Adeline E. Williams, Irma Sánchez-Vargas, Jing‐Yi Lin, Rucsanda Juncu, Ken E. Olson, Alexander W. E. FranzList of authors in order
- Landing page
-
https://doi.org/10.1093/g3journal/jkac280Publisher landing page
- PDF URL
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https://academic.oup.com/g3journal/article-pdf/12/12/jkac280/47467940/jkac280.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/g3journal/article-pdf/12/12/jkac280/47467940/jkac280.pdfDirect OA link when available
- Concepts
-
Biology, Gene drive, Genetics, CRISPR, Locus (genetics), Effector, Population, Gene, Cas9, Aedes aegypti, Cell biology, Demography, Sociology, Larva, BotanyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
32Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 9, 2023: 12, 2022: 2Per-year citation counts (last 5 years)
- References (count)
-
56Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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