Bioinformatic and cell-based tools for pooled CRISPR knockout screening in mosquitos.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 11 2021
Historique:
received: 18 04 2021
accepted: 02 11 2021
entrez: 25 11 2021
pubmed: 26 11 2021
medline: 24 12 2021
Statut: epublish

Résumé

Mosquito-borne diseases present a worldwide public health burden. Current efforts to understand and counteract them have been aided by the use of cultured mosquito cells. Moreover, application in mammalian cells of forward genetic approaches such as CRISPR screens have identified essential genes and genes required for host-pathogen interactions, and in general, aided in functional annotation of genes. An equivalent approach for genetic screening of mosquito cell lines has been lacking. To develop such an approach, we design a new bioinformatic portal for sgRNA library design in several mosquito genomes, engineer mosquito cell lines to express Cas9 and accept sgRNA at scale, and identify optimal promoters for sgRNA expression in several mosquito species. We then optimize a recombination-mediated cassette exchange system to deliver CRISPR sgRNA and perform pooled CRISPR screens in an Anopheles cell line. Altogether, we provide a platform for high-throughput genome-scale screening in cell lines from disease vector species.

Identifiants

pubmed: 34819517
doi: 10.1038/s41467-021-27129-3
pii: 10.1038/s41467-021-27129-3
pmc: PMC8613219
doi:

Substances chimiques

RNA, Guide 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6825

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM132087
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

World Health Organization. World Malaria Report 2020: 20 years of global progress and challenges. Geneva: World Health Organization; Licence: CC BY-NC-SA 3.0 IGO. (2020).
Bhatt, S. et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 526, 207–211 (2015).
pubmed: 26375008 pmcid: 4820050 doi: 10.1038/nature15535
Wilson, A. L. et al. The importance of vector control for the control and elimination of vector-borne diseases. PLoS Negl. Trop. Dis. 14, e0007831 (2020).
pubmed: 31945061 pmcid: 6964823 doi: 10.1371/journal.pntd.0007831
Ranson, H. & Lissenden, N. Insecticide resistance in African Anopheles mosquitoes: A worsening situation that needs urgent action to maintain malaria control. Trends. Parasitol. 32, 187–196 (2016).
pubmed: 26826784 doi: 10.1016/j.pt.2015.11.010
Dusfour, I. et al. Management of insecticide resistance in the major Aedes vectors of arboviruses: Advances and challenges. PLoS Negl. Trop. Dis. 13, 1–22 (2019).
doi: 10.1371/journal.pntd.0007615
Flores, H. A. & O’Neill, S. L. Controlling vector-borne diseases by releasing modified mosquitoes. Nat. Rev. Microbiol. 16, 508–518 (2018).
pubmed: 29777177 pmcid: 7612058 doi: 10.1038/s41579-018-0025-0
Shaw, W. R. & Catteruccia, F. Vector biology meets disease control: using basic research to fight vector-borne diseases. Nat. Microbiol. 4, 20–34 (2019).
pubmed: 30150735 doi: 10.1038/s41564-018-0214-7
Iturbe-Ormaetxe, I., Walker, T. & O’Neill, S. L. Wolbachia and the biological control of mosquito-borne disease. EMBO. Rep. 12, 508–518 (2011).
pubmed: 21546911 pmcid: 3128286 doi: 10.1038/embor.2011.84
Utarini, A. et al. Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue. N. Engl. J. Med. 384, 2177–2186 (2021).
pubmed: 34107180 pmcid: 8103655 doi: 10.1056/NEJMoa2030243
Hammond, A. et al. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat. Biotechnol. 34, 78–83 (2015).
pubmed: 26641531 pmcid: 4913862 doi: 10.1038/nbt.3439
Kyrou, K. et al. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat. Biotechnol. 36, 1062–1071 (2018).
pubmed: 30247490 pmcid: 6871539 doi: 10.1038/nbt.4245
Gantz, V. M. et al. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc. Natl. Acad. Sci. U. S. A. 112, E6736–E6743 (2015).
pubmed: 26598698 pmcid: 4679060 doi: 10.1073/pnas.1521077112
Adolfi, A. et al. Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi. Nat. Commun. 11, 5553 (2020).
pubmed: 33144570 pmcid: 7609566 doi: 10.1038/s41467-020-19426-0
Carballar-Lejarazú, R. et al. Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae. Proc. Natl. Acad. Sci. U. S. A. 117, 22805–22814 (2020).
pubmed: 32839345 pmcid: 7502704 doi: 10.1073/pnas.2010214117
Ford, K., McDonald, D. & Mali, P. Functional genomics via CRISPR–Cas. J. Mol. Biol. 431, 48–65 (2019).
pubmed: 29959923 doi: 10.1016/j.jmb.2018.06.034
Doerflinger, M., Forsyth, W., Ebert, G., Pellegrini, M. & Herold, M. J. CRISPR/Cas9—The ultimate weapon to battle infectious diseases? Cell. Microbiol. 19, 1–10 (2017).
doi: 10.1111/cmi.12693
Puschnik, A. S., Majzoub, K., Ooi, Y. S. & Carette, J. E. A CRISPR toolbox to study virus-host interactions. Nat. Rev. Microbiol. 15, 351–364 (2017).
pubmed: 28420884 pmcid: 5800792 doi: 10.1038/nrmicro.2017.29
Zhang, R. et al. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature 535, 164–168 (2016).
pubmed: 27383988 pmcid: 4945490 doi: 10.1038/nature18625
Ma, H. et al. A CRISPR-based screen identifies genes essential for west-nile-virus-induced cell death. Cell. Rep. 12, 673–683 (2015).
pubmed: 26190106 pmcid: 4559080 doi: 10.1016/j.celrep.2015.06.049
Filomatori, C. V. et al. Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells. PLoS. Pathog. 13, 1–23 (2017).
doi: 10.1371/journal.ppat.1006265
Blair, C. D. Mosquito RNAi is the major innate immune pathway controlling arbovirus infection and transmission. Future Microbiol. 6, 265–277 (2011).
pubmed: 21449839 doi: 10.2217/fmb.11.11
Tassetto, M. et al. Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements. Elife 8, 1–29 (2019).
doi: 10.7554/eLife.41244
Jose, J., Taylor, A. B. & Kuhn, R. J. Spatial and Temporal Analysis of Alphavirus Replication and Assembly in Mammalian and Mosquito Cells. MBio 8, e02294–16 (2017).
pubmed: 28196962 pmcid: 5312085 doi: 10.1128/mBio.02294-16
Walker, T., Jeffries, C. L., Mansfield, K. L. & Johnson, N. Mosquito cell lines: History, isolation, availability and application to assess the threat of arboviral transmission in the United Kingdom. Parasites Vectors 7, 1–9 (2014).
doi: 10.1186/1756-3305-7-382
Acosta, E. G., Castilla, V. & Damonte, E. B. Infectious dengue-1 virus entry into mosquito C6/36 cells. Virus Res. 160, 173–179 (2011).
pubmed: 21708195 doi: 10.1016/j.virusres.2011.06.008
Londono-Renteria, B. et al. Dengue virus infection of aedes aegypti requires a putative cysteine rich venom protein. PLoS. Pathog. 11, 1–23 (2015).
doi: 10.1371/journal.ppat.1005202
Lombardo, F., Ghani, Y., Kafatos, F. C. & Christophides, G. K. Comprehensive Genetic Dissection of the Hemocyte Immune Response in the Malaria Mosquito Anopheles gambiae. PLoS Pathog. 9, e1003145 (2013).
pubmed: 23382679 pmcid: 3561300 doi: 10.1371/journal.ppat.1003145
Schnettler, E. et al. Knockdown of piRNA pathway proteins results in enhanced semliki forest virus production in mosquito cells. J. Gen. Virol. 94, 1680–1689 (2013).
pubmed: 23559478 pmcid: 3709635 doi: 10.1099/vir.0.053850-0
Ma, Q. et al. A mosquito small RNA genomics resource reveals dynamic evolution and host responses to viruses and transposons. Genome Res. Gr. 265157, 120 (2021).
Sakamoto, J. M. & Azad, A. F. Propagation of arthropod-borne Rickettsia spp. in two mosquito cell lines. Appl. Environ. Microbiol. 73, 6637–6643 (2007).
pubmed: 17766452 pmcid: 2075076 doi: 10.1128/AEM.00923-07
O’Neal, M. A., Posner, B. A., Coates, C. J. & Abrams, J. M. A cell-based screening platform identifies novel mosquitocidal toxins. J. Biomol. Screen. 18, 688–694 (2013).
pubmed: 23407365 pmcid: 3687004 doi: 10.1177/1087057113476952
Kuadkitkan, A., Smith, D. R. & Berry, C. Investigation of the cry4B-prohibitin interaction in Aedes aegypti cells. Curr. Microbiol. 65, 446–454 (2012).
pubmed: 22767320 doi: 10.1007/s00284-012-0178-4
Öhlund, P., Lundén, H. & Blomström, A. L. Insect-specific virus evolution and potential effects on vector competence. Virus Genes. 55, 127–137 (2019).
pubmed: 30632016 pmcid: 6458977 doi: 10.1007/s11262-018-01629-9
Hughes, G. L. et al. Wolbachia Infections in Anopheles gambiae Cells: Transcriptomic Characterization of a Novel Host-Symbiont Interaction. PLoS Pathog. 7, e1001296 (2011).
pubmed: 21379333 pmcid: 3040664 doi: 10.1371/journal.ppat.1001296
Rozen-Gagnon, K., Yi, S., Jacobson, E., Novack, S. & Rice, C. M. A selectable, plasmid-based system to generate CRISPR/Cas9 gene edited and knock-in mosquito cell lines. Sci. Rep. 11, 1–14 (2021).
Varjak, M., Kean, J., Vazeille, M., Failloux, A. & Kohl, A. Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses. mSphere 2, e00144–17 (2017).
pubmed: 28497119 pmcid: 5415634 doi: 10.1128/mSphere.00144-17
Azlan, A., Obeidat, S. M., Das, K. T., Yunus, M. A. & Azzam, G. Genome-wide identification of aedes albopictus long noncoding rnas and their association with dengue and zika virus infection. PLoS Negl. Trop. Dis. 15, 1–20 (2021).
doi: 10.1371/journal.pntd.0008351
Feng, X. et al. Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes. Nat. Commun. 12, 2960 (2021).
pubmed: 34017003 pmcid: 8137705 doi: 10.1038/s41467-021-23239-0
Anderson, M. A. E. et al. Expanding the CRISPR Toolbox in Culicine Mosquitoes: In Vitro Validation of Pol III Promoters. ACS Synth. Biol. 9, 678–681 (2020).
pubmed: 32129976 pmcid: 7093051 doi: 10.1021/acssynbio.9b00436
Viswanatha, R., Li, Z., Hu, Y. & Perrimon, N. Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in Drosophila cells. Elife 7, 1–20 (2018).
doi: 10.7554/eLife.36333
Giannoni, F. et al. Nuclear factors bind to a conserved DNA element that modulates transcription of Anopheles gambiae trypsin genes. J. Biol. Chem. 276, 700–707 (2001).
pubmed: 11016929 doi: 10.1074/jbc.M005540200
Hu, Y. et al. An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinformatics 12, 357 (2011).
pubmed: 21880147 pmcid: 3179972 doi: 10.1186/1471-2105-12-357
Housden, B. E. et al. Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi. Sci. Signal. 8, 1–10 (2015).
doi: 10.1126/scisignal.aab3729
Viswanatha, R. et al. Pooled CRISPR Screens in Drosophila Cells. Curr. Protoc. Mol. Biol. 129, 1–21 (2019).
doi: 10.1002/cpmb.111
The Anopheles gambiae 1000 Genomes Consortium. Ag1000G phase 2 AR1 data release. MalariaGEN. http://www.malariagen.net/data/ag1000g-phase2-ar1 (2017).
Miles, A. et al. Genetic diversity of the African malaria vector anopheles gambiae. Nature. 552, 96–100 (2017).
doi: 10.1038/nature24995
Coetzee, M. et al. Anopheles coluzzii and anopheles amharicus, new members of the anopheles gambiae complex. Zootaxa 3619, 246–274 (2013).
pubmed: 26131476 doi: 10.11646/zootaxa.3619.3.2
Hsu, S. H., Mao, W. H. & Cross, J. H. Establishment of a line of cells derived from ovarian tissue of Culex quinquefasciatus Say. J. Med. Entomol. 7, 703–707 (1970).
pubmed: 5501238 doi: 10.1093/jmedent/7.6.703
Igarashi, A. Isolation of a Singh’s Aedes albopictus cell clone sensitive to dengue and Chikungunya viruses. J. Gen. Virol. 40, 531–544 (1978).
pubmed: 690610 doi: 10.1099/0022-1317-40-3-531
Neumüller, R. A. et al. Stringent analysis of gene function and protein-protein interactions using fluorescently tagged genes. Genetics 190, 931–940 (2012).
pubmed: 22174071 pmcid: 3296255 doi: 10.1534/genetics.111.136465
Venken, K. J. T. et al. MiMIC: A highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat. Methods 8, 737–747 (2011).
pubmed: 21985007 pmcid: 3191940 doi: 10.1038/nmeth.1662
Zhu, S. et al. Guide RNAs with embedded barcodes boost CRISPR-pooled screens. Genome Biol. 20, 1–12 (2019).
doi: 10.1186/s13059-019-1628-0
Michlits, G. et al. CRISPR-UMI: Single-cell lineage tracing of pooled CRISPR-Cas9 screens. Nat. Methods 14, 1191–1197 (2017).
pubmed: 29039415 doi: 10.1038/nmeth.4466
Schmierer, B. et al. CRISPR/Cas9 screening using unique molecular identifiers. Mol. Syst. Biol. 13, 945 (2017).
pubmed: 28993443 pmcid: 5658704 doi: 10.15252/msb.20177834
Konet, D. S. et al. Short-hairpin RNA expressed from polymerase III promoters mediates RNA interference in mosquito cells. Insect Mol. Biol. 16, 199–206 (2007).
pubmed: 17298556 doi: 10.1111/j.1365-2583.2006.00714.x
Li, M. et al. Development of a confinable gene drive system in the human disease vector aedes aegypti. Elife 9, 1–22 (2020).
Rogers, S. L. & Rogers, G. C. Culture of Drosophila S2 cells and their use for RNAi-mediated loss-of-function studies and immunofluorescence microscopy. Nat. Protoc. 3, 606–611 (2008).
pubmed: 18388942 doi: 10.1038/nprot.2008.18
Shah, P. S. et al. Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis. Cell 1931–1945 (2018).
Teramoto, T., Huang, X., Armbruster, P. A. & Padmanabhan, R. Infection of Aedes albopictus Mosquito C6/36 Cells with the wMelpop Strain of Wolbachia Modulates Dengue Virus-Induced Host Cellular Transcripts and Induces Critical Sequence Alterations in the Dengue Viral Genome. J. Virol. 93, 1–21 (2019).
doi: 10.1128/JVI.00581-19
Li, M. J. et al. Transcriptome analysis of Aedes aegypti Aag2 cells in response to dengue virus-2 infection. Parasites and Vectors 13, 1–14 (2020).
doi: 10.1186/s13071-020-04294-w
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184–191 (2016).
pubmed: 26780180 pmcid: 4744125 doi: 10.1038/nbt.3437
Gebre, M., Nomburg, J. L. & Gewurz, B. E. Crispr–Cas9 genetic analysis of virus–Host interactions. Viruses 10, 1–22 (2018).
doi: 10.3390/v10020055
Oberhofer, G., Ivy, T. & Hay, B. A. Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs. Proc. Natl. Acad. Sci. U. S. A 115, E9343–E9352 (2018).
pubmed: 30224454 pmcid: 6176634 doi: 10.1073/pnas.1805278115
Port, F., Chen, H.-M., Lee, T. & Bullock, S. L. Optimized CRISPR/Cas tools for efficient germline and somatic genome engineering in Drosophila. Proc. Natl. Acad. Sci. 111, E2967–E2976 (2014).
pubmed: 25002478 pmcid: 4115528 doi: 10.1073/pnas.1405500111
Okamoto, N. et al. A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila. Dev. Cell. 47, 294–305.e7 (2018).
pubmed: 30293839 pmcid: 6219898 doi: 10.1016/j.devcel.2018.09.012
Esvelt, K. M., Smidler, A. L., Catteruccia, F. & Church, G. M. Concerning RNA-guided gene drives for the alteration of wild populations. Elife 3, e03401 (2014).
pubmed: 25035423 pmcid: 4117217 doi: 10.7554/eLife.03401
Sessions, O. M. et al. Discovery of insect and human dengue virus host factors. Nature 458, 1047–1050 (2009).
pubmed: 19396146 pmcid: 3462662 doi: 10.1038/nature07967
Yasunaga, A. et al. Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection. PLoS Pathog. 10, e1003914 (2014).
pubmed: 24550726 pmcid: 3923753 doi: 10.1371/journal.ppat.1003914
Madeira, F. et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 47, W636–W641 (2019).
pubmed: 30976793 pmcid: 6602479 doi: 10.1093/nar/gkz268
Waterhouse, A. M., Procter, J. B., Martin, D. M. A., Clamp, M. & Barton, G. J. Jalview Version 2-A multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191 (2009).
pubmed: 19151095 pmcid: 2672624 doi: 10.1093/bioinformatics/btp033
Gao, Z., Herrera-Carrillo, E. & Berkhout, B. Delineation of the exact transcription termination signal for Type 3 Polymerase III. Mol. Ther. - Nucleic Acids 10, 36–44 (2018).
pubmed: 29499947 doi: 10.1016/j.omtn.2017.11.006
Bryksin, A. V. & Matsumura, I. Overlap extension PCR cloning: A simple and reliable way to create recombinant plasmids. Biotechniques 48, 463–465 (2010).
pubmed: 20569222 pmcid: 3121328 doi: 10.2144/000113418
Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).
pubmed: 24157548 pmcid: 3969860 doi: 10.1038/nprot.2013.143
Anderson, M. A. E., Gross, T. L., Myles, K. M. & Adelman, Z. N. Validation of novel promoter sequences derived from two endogenous ubiquitin genes in transgenic Aedes aegypti. Insect Mol. Biol. 19, 441–449 (2010).
pubmed: 20456509 pmcid: 3605713
Santolamazza, F. et al. Insertion polymorphisms of SINE200 retrotransposons within speciation islands of Anopheles gambiae molecular forms. Malar. J. 7, 1–10 (2008).
doi: 10.1186/1475-2875-7-163
Schwartz, J. J., Lee, C. & Shendure, J. Accurate gene synthesis with tag-directed retrieval of sequence-verified DNA molecules. Nat. Methods 9, 913–915 (2012).
pubmed: 22886093 pmcid: 3433648 doi: 10.1038/nmeth.2137
Clarkson, C. S. et al. Genome variation and population structure among 1142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii. Genome. Res. 30, 1533–1546 (2020).
doi: 10.1101/gr.262790.120

Auteurs

Raghuvir Viswanatha (R)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA. ram@genetics.med.harvard.edu.

Enzo Mameli (E)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Department of Microbiology, National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, 620 Albany Street, Boston, MA, 02118, USA.

Jonathan Rodiger (J)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.

Pierre Merckaert (P)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.

Fabiana Feitosa-Suntheimer (F)

Department of Microbiology, National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, 620 Albany Street, Boston, MA, 02118, USA.

Tonya M Colpitts (TM)

Department of Microbiology, National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, 620 Albany Street, Boston, MA, 02118, USA.

Stephanie E Mohr (SE)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.

Yanhui Hu (Y)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.

Norbert Perrimon (N)

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA. perrimon@receptor.med.harvard.edu.
HHMI, Harvard Medical School, Boston, MA, 02115, USA. perrimon@receptor.med.harvard.edu.

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