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A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae
Open accessAbstract
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
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Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Efficient genome editing in zebrafish using a CRISPR-Cas system
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J.-R. J., & Joung, J. K. (2013) · Nature Biotechnology · doi:10.1038/nbt.2501 · Cited by 2,937
Improving CRISPR-Cas nuclease specificity using truncated guide RNAs
Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., & Joung, J. K. (2014) · Nature Biotechnology · doi:10.1038/nbt.2808 · Cited by 1,993
Optimized CRISPR/Cas tools for efficient germline and somatic genome engineering in Drosophila
Port, F., Chen, H.-M., Lee, T., & Bullock, S. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405500111 · Cited by 1,046
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Ricciardi, A., Blackburn, T. M., Carlton, J. T., Dick, J. T. A., Hulme, P. E., Iacarella, J. C., Jeschke, J. M., Liebhold, A. M., Lockwood, J. L., MacIsaac, H. J., et al. (2017) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2017.03.007 · Cited by 458
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Theissinger, K., Fernandes, C., Formenti, G., Bista, I., Berg, P. R., Bleidorn, C., Bombarely, A., Crottini, A., Gallo, G. R., Godoy, J. A., et al. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.01.005 · Cited by 401
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Metadata
- Authors
- Hammond, A., Galizi, R., Kyrou, K., Simoni, A., Siniscalchi, C., Katsanos, D., Gribble, M., Baker, D., Marois, E., Russell, S., Burt, A., Windbichler, N., Crisanti, A., & Nolan, T.
- Venue
- Nature Biotechnology
- Published
- 2016-01
- Volume
- 34
- Issue
- 1
- Pages
- 78-83
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2190054909
- Cited by
- 1,165
- References
- 5
- FWCI
- 42.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hammond, A., Galizi, R., Kyrou, K., Simoni, A., Siniscalchi, C., Katsanos, D., Gribble, M., Baker, D., Marois, E., Russell, S., Burt, A., Windbichler, N., Crisanti, A., & Nolan, T. (2016). A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology. https://doi.org/10.1038/nbt.3439
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