Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells

<b>Background/Objectives</b>: <i>Culex</i> species mosquitoes are globally distributed and transmit several pathogens that impact animal and public health, including West Nile virus, Usutu virus, and <i>Plasmodium relictum</i>. Despite their relevance, <i>Cu...

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Main Authors: Elizabeth Walsh, Tran Zen B. Torres, Brian C. Prince, Claudia Rückert
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:DNA
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Online Access:https://www.mdpi.com/2673-8856/5/1/1
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author Elizabeth Walsh
Tran Zen B. Torres
Brian C. Prince
Claudia Rückert
author_facet Elizabeth Walsh
Tran Zen B. Torres
Brian C. Prince
Claudia Rückert
author_sort Elizabeth Walsh
collection DOAJ
description <b>Background/Objectives</b>: <i>Culex</i> species mosquitoes are globally distributed and transmit several pathogens that impact animal and public health, including West Nile virus, Usutu virus, and <i>Plasmodium relictum</i>. Despite their relevance, <i>Culex</i> species are less widely studied than <i>Aedes</i> and <i>Anopheles</i> mosquitoes. To expand the genetic tools used to study <i>Culex</i> mosquitoes, we previously developed an optimized plasmid for transient Cas9 and single-guide RNA (sgRNA) expression in <i>Culex quinquefasciatus</i> cells to generate gene knockouts. Here, we established a monoclonal cell line that consistently expresses Cas9 and can be used for screens to determine gene function or antiviral activity. <b>Methods</b>: We used this system to perform the successful gene editing of seven genes and subsequent testing for potential antiviral effects, using a simple single-guide RNA (sgRNA) transfection and subsequent virus infection. <b>Results</b>: We were able to show antiviral effects for the <i>Cx. quinquefasciatus</i> genes <i>dicer-2</i>, <i>argonaute-2b</i>, <i>vago</i>, <i>piwi5</i>, <i>piwi6a</i>, and <i>cullin4a</i>. In comparison to the RNAi-mediated gene silencing of <i>dicer-2</i>, <i>argonaute-2b</i>, and <i>piwi5</i>, our Cas9/sgRNA approach showed an enhanced ability to detect antiviral effects. <b>Conclusions</b>: We propose that this cell line offers a new tool for studying gene function in <i>Cx. quinquefasciatus</i> mosquitoes that avoids the use of RNAi. This short study also serves as a proof-of-concept for future gene knock-ins in these cells. Our cell line expands the molecular resources available for vector competence research and will support the design of future research strategies to reduce the transmission of mosquito-borne diseases.
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spelling doaj-art-bfac506fd06c4c0d857d78e9e7717bf62025-08-20T02:42:42ZengMDPI AGDNA2673-88562025-01-0151110.3390/dna5010001Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito CellsElizabeth Walsh0Tran Zen B. Torres1Brian C. Prince2Claudia Rückert3Department of Biochemistry and Molecular Biology, College of Agriculture, Biotechnology & Natural Resources, University of Nevada, Reno, NV 89557, USADepartment of Biochemistry and Molecular Biology, College of Agriculture, Biotechnology & Natural Resources, University of Nevada, Reno, NV 89557, USADepartment of Biochemistry and Molecular Biology, College of Agriculture, Biotechnology & Natural Resources, University of Nevada, Reno, NV 89557, USADepartment of Biochemistry and Molecular Biology, College of Agriculture, Biotechnology & Natural Resources, University of Nevada, Reno, NV 89557, USA<b>Background/Objectives</b>: <i>Culex</i> species mosquitoes are globally distributed and transmit several pathogens that impact animal and public health, including West Nile virus, Usutu virus, and <i>Plasmodium relictum</i>. Despite their relevance, <i>Culex</i> species are less widely studied than <i>Aedes</i> and <i>Anopheles</i> mosquitoes. To expand the genetic tools used to study <i>Culex</i> mosquitoes, we previously developed an optimized plasmid for transient Cas9 and single-guide RNA (sgRNA) expression in <i>Culex quinquefasciatus</i> cells to generate gene knockouts. Here, we established a monoclonal cell line that consistently expresses Cas9 and can be used for screens to determine gene function or antiviral activity. <b>Methods</b>: We used this system to perform the successful gene editing of seven genes and subsequent testing for potential antiviral effects, using a simple single-guide RNA (sgRNA) transfection and subsequent virus infection. <b>Results</b>: We were able to show antiviral effects for the <i>Cx. quinquefasciatus</i> genes <i>dicer-2</i>, <i>argonaute-2b</i>, <i>vago</i>, <i>piwi5</i>, <i>piwi6a</i>, and <i>cullin4a</i>. In comparison to the RNAi-mediated gene silencing of <i>dicer-2</i>, <i>argonaute-2b</i>, and <i>piwi5</i>, our Cas9/sgRNA approach showed an enhanced ability to detect antiviral effects. <b>Conclusions</b>: We propose that this cell line offers a new tool for studying gene function in <i>Cx. quinquefasciatus</i> mosquitoes that avoids the use of RNAi. This short study also serves as a proof-of-concept for future gene knock-ins in these cells. Our cell line expands the molecular resources available for vector competence research and will support the design of future research strategies to reduce the transmission of mosquito-borne diseases.https://www.mdpi.com/2673-8856/5/1/1Cas9gene editinggene knock-inarbovirusesmosquitoescell lines
spellingShingle Elizabeth Walsh
Tran Zen B. Torres
Brian C. Prince
Claudia Rückert
Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
DNA
Cas9
gene editing
gene knock-in
arboviruses
mosquitoes
cell lines
title Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
title_full Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
title_fullStr Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
title_full_unstemmed Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
title_short Generation of Cas9 Knock-In <i>Culex quinquefasciatus</i> Mosquito Cells
title_sort generation of cas9 knock in i culex quinquefasciatus i mosquito cells
topic Cas9
gene editing
gene knock-in
arboviruses
mosquitoes
cell lines
url https://www.mdpi.com/2673-8856/5/1/1
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