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HomeNatureDriving a protective allele of the mosquito FREP1 gene to combat malaria

Driving a protective allele of the mosquito FREP1 gene to combat malaria

  • World Malaria Report 2024: Addressing Inequity in the Global Malaria Response (World Health Organization, 2024).

  • Zhang, G. et al. Anopheles midgut FREP1 mediates Plasmodium invasion. J. Biol. Chem. 290, 16490–16501 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, J. et al. Genome-block expression-assisted association studies discover malaria resistance genes in Anopheles gambiae. Proc. Natl Acad. Sci. USA 110, 20675–20680 (2013).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Unwin, H. J. T., Sherrard-Smith, E., Churcher, T. S. & Ghani, A. C. Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria. Nat. Commun. 14, 676 (2023).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, S. & Jacobs-Lorena, M. Genetic approaches to interfere with malaria transmission by vector mosquitoes. Trends Biotechnol. 31, 185–193 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, Y., Simões, M. L. & Dimopoulos, G. Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles. Sci. Adv. 6, eaay5898 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoermann, A. et al. Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development. Sci. Adv. 8, eabo1733 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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. USA 112, E6736–E6743 (2015).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • James, A. A. Gene drive systems in mosquitoes: rules of the road. Trends Parasitol. 21, 64–67 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Adolfi, A. et al. Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi. Nat. Commun. 11, 5553 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Collins, F. H. et al. Genetic selection of a Plasmodium-refractory strain of the malaria vector Anopheles gambiae. Science 234, 607–610 (1986).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Simões, M. L., Dong, Y., Mlambo, G. & Dimopoulos, G. C-type lectin 4 regulates broad-spectrum melanization-based refractoriness to malaria parasites. PLoS Biol. 20, e3001515 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, Y., Simões, M. L., Marois, E. & Dimopoulos, G. CRISPR/Cas9-mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection. PLoS Pathog. 14, e1006898 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Isaacs, A. T. et al. Engineered resistance to Plasmodium falciparum development in transgenic Anopheles stephensi. PLoS Pathog. 7, e1002017 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niu, G. et al. Targeting mosquito FREP1 with a fungal metabolite blocks malaria transmission. Sci. Rep. 5, 14694 (2015).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moreira, L. A. et al. Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes. J. Biol. Chem. 277, 40839–40843 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • Dong, Y. et al. Engineered anopheles immunity to Plasmodium infection. PLoS Pathog. 7, e1002458 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kang, S., Shields, A. R., Jupatanakul, N. & Dimopoulos, G. Suppressing dengue-2 infection by chemical inhibition of Aedes aegypti host factors. PLoS Negl. Trop. Dis. 8, e3084 (2014).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gantz, V. M. & Akbari, O. S. Gene editing technologies and applications for insects. Curr. Opin. Insect Sci. 28, 66–72 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Osta, M. A., Christophides, G. K. & Kafatos, F. C. Effects of mosquito genes on Plasmodium development. Science 303, 2030–2032 (2004).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Isaacs, A. T. et al. Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development. Proc. Natl Acad. Sci. USA 109, E1922–E1930 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carballar-Lejarazú, R. et al. Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii. Proc. Natl Acad. Sci. USA 120, e2221118120 (2023).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dilani, P. V. D., Dassanayake, R. S., Tyagi, B. K. & Gunawardene, Y. I. N. S. The impact of transgenesis on mosquito fitness: a review. Front. Insect Sci. 2, 957570 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marrelli, M. T., Moreira, C. K., Kelly, D., Alphey, L. & Jacobs-Lorena, M. Mosquito transgenesis: what is the fitness cost? Trends Parasitol. 22, 197–202 (2006).

    PubMed 

    Google Scholar
     

  • Abraham, E. G. et al. Driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with AgAper1 regulatory elements. Insect Mol. Biol. 14, 271–279 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Carballar-Lejarazú, R. et al. Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae. Proc. Natl Acad. Sci. USA 117, 22805–22814 (2020).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bennink, S., Kiesow, M. J. & Pradel, G. The development of malaria parasites in the mosquito midgut. Cell. Microbiol. 18, 905–918 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, S., Dong, Y., Simões, M. L. & Dimopoulos, G. Mosquito transgenesis for malaria control. Trends Parasitol. 38, 54–66 (2022).

    CAS 
    PubMed 

    Google Scholar
     

  • Dong, Y. et al. Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathog. 2, e52 (2006).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, Y. & Dimopoulos, G. Anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites. J. Biol. Chem. 284, 9835–9844 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Symington, L. S. & Gautier, J. Double-strand break end resection and repair pathway choice. Annu. Rev. Genet. 45, 247–271 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Sfeir, A. & Symington, L. S. Microhomology-mediated end joining: a back-up survival mechanism or dedicated pathway? Trends Biochem. Sci. 40, 701–714 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bazzano, D., Lomonaco, S. & Wilson, T. E. Mapping yeast mitotic 5′ resection at base resolution reveals the sequence and positional dependence of nucleases in vivo. Nucleic Acids Res. 49, 12607–12621 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cejka, P. & Symington, L. S. DNA end resection: mechanism and control. Annu. Rev. Genet. 55, 285–307 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • Yannuzzi, I., Butler, M. A., Fernandez, J. & Larocque, J. R. The role of Drosophila CtIP in homology-directed repair of DNA double-strand breaks. Genes 12, 1430 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xi, Z., Das, S., Garver, L. & Dimopoulos, G. Protocol for Plasmodium falciparum infections in mosquitoes and infection phenotype determination. J. Vis. Exp. 5, 222 (2007).

  • Kanatani, S., Stiffler, D., Bousema, T., Yenokyan, G. & Sinnis, P. Revisiting the Plasmodium sporozoite inoculum and elucidating the efficiency with which malaria parasites progress through the mosquito. Nat. Commun. 15, 748 (2024).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niu, G. et al. The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen. J. Biol. Chem. 292, 11960–11969 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, X. et al. Active-genetic neutralizing elements for halting or deleting gene-drives. Mol. Cell 80, 246–262 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, G., Niu, G., Perez, L., Wang, X. & Li, J. Malaria transmission assisted by interaction between Plasmodium α-tubulin-1 and Anopheles FREP1 protein. Preprint at bioRxiv https://doi.org/10.1101/2019.12.16.878082.

  • Corby-Harris, V. et al. Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi mosquitoes. PLoS Pathog. 6, e1001003 (2010).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guichard, A. et al. Efficient allelic-drive in Drosophila. Nat. Commun. 10, 1640 (2019).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaduskar, B. et al. Reversing insecticide resistance with allelic-drive in Drosophila melanogaster. Nat. Commun. 13, 291 (2022).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bier, E. Gene drives gaining speed. Nat. Rev. Genet. 23, 5–22 (2022).

    CAS 
    PubMed 

    Google Scholar
     

  • Gantz, V. M. & Bier, E. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science 348, 442–444 (2015).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Z. et al. CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion. Nat. Commun. 12, 2625 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Terradas, G. et al. Inherently confinable split-drive systems in Drosophila. Nat. Commun. 12, 1480 (2021).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Terradas, G., Bennett, J. B., Li, Z., Marshall, J. M. & Bier, E. Genetic conversion of a split-drive into a full-drive element. Nat. Commun. 14, 191 (2023).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • DiCarlo, J. E., Chavez, A., Dietz, S. L., Esvelt, K. M. & Church, G. M. Safeguarding CRISPR–Cas9 gene drives in yeast. Nat. Biotechnol. 33, 1250–1255 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • Kyrou, K. et al. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat. Biotechnol. 36, 1062–1066 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Walter, M. & Verdin, E. Viral gene drive in herpesviruses. Nat. Commun. 11, 4884 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Valderrama, J. A., Kulkarni, S. S., Nizet, V. & Bier, E. A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus. Nat. Commun. 10, 5276 (2019).


    Google Scholar
     

  • Auradkar, A., Corder, M. R., Marshall, M. J. & Bier, E. A self-eliminating allelic-drive reverses insecticide resistance in Drosophila leaving no transgene in the population. Nat. Commun. 15, 9961 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • López Del Amo, V. et al. A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment. Nat. Commun. 11, 352 (2020).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nash, A. et al. Integral gene drives for population replacement. Biol. Open 8, bio037762 (2018).

    PubMed Central 

    Google Scholar
     

  • Nash, A., Capriotti, P., Hoermann, A., Papathanos, P. A. & Windbichler, N. Intronic gRNAs for the construction of minimal gene drive systems. Front. Bioeng. Biotechnol. 10, 857460 (2022).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chakraborty, M. et al. Hidden features of the malaria vector mosquito, Anopheles stephensi, revealed by a high-quality reference genome. BMC Biol. 19, 28 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Z. et al. Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier. Nat. Commun. 15, 2629 (2024).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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