Abstract
Advancements in genetic engineering have resulted in the development of mosquitoes with impaired vector competence, thereby limiting acquisition and transmission of pathogens. The main dengue (DENV) vector, Aedes aegypti, is an invasive species that have spread unwittingly across the world as a result of human trade and travel. The Ae. aegypti mosquito species has spread across tropical and subtropical regions, with higher presence in urban regions where rapid breeding patterns have shown in artificial containers. Identification of and treating an adequate number of mosquito breeding sites as a control measure have been done for the past couple of years, and yet improvement is far from the expectations, even with well-funded and well-organized initiatives. In order to stop the pathogen transmission, genetically modified mosquitoes (GMM) needs to be created and released. Despite many Aedes-related achievements, GMM creation has been challenging. The spread of particular genetic elements that impair vector competence, trigger deleterious recessive mutations, or skew a population's sex ratio can be used to prevent the spread of vector disease, or eradicate invasive organisms in a species-specific and eco-friendly manner. In recent years, genome editing strategies have evolved to make use of a variety of nucleases, ranging from sequence-specific zinc finger nucleases to modular TALENs (transcription activator-like effector nucleases) and most recently, RNA-guided nucleases adapted from bacterial adaptive immune systems, dubbed CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR associated systems). By combining these methods, a new era in gene editing had emerged. Generally, both of these gene editing technologies utilize sequence-specific nucleases to generate double-stranded DNA breaks (or nicks) in the target sequence, resulting in desired DNA modifications using endogenous DNA repair mechanisms. Since cells with DNA lesions are unable to divide further, the nuclease-generated strand breaks must be rapidly repaired by the cell to maintain the viability. CRISPR/Cas has been widely accepted for use in a variety of organisms, including insect species, with only minor optimization steps needed thus far. CRISPR/Cas9 technology transformed the process of engineering nucleases capable of cleaving complex genomic sequences. A complementary guide RNA (gRNA) directs the Cas9 endonuclease's operation to the specific DNA target site, enabling the editing of virtually any DNA sequence without complex protein engineering and selection procedures. Apart from genome editing, the specificity and flexibility of the CRISPR/Cas9 method enables unprecedented rapid development of genetically modified organisms with mutation systems for disease vector insect control. The stability and expression of the gene construct generated by CRISPR/Cas9 or any other method must be addressed before GMM are released, in order to make sure that pathogen transmission and formulation are interrupted robustly and completely. Spreading foreign antipathogen genes through gene drive strategies among wild mosquito populations strengthens the case for a more streamlined approach. Major fields that must be adequately assessed include risk evaluation and management, conducting studies to ensure human and environmental protection, developing effective control strategies built on comprehensive gene-driving systems, and adequately addressing the ethical, legal, and social consequences of GMM release. Although GMM is theoretically feasible as a disease control method, field releases should be made only when strong scientific evidence of human and environmental protection and effectiveness are presented, and public acceptance is addressed appropriately. This chapter discusses the diverse technological advances in generating Ae. aegypti mosquitoes which are resistant to dengue virus (DENV) and other diseases, as well as the biosafety and risk assessment of these procedures. Additionally, the chapter outlines a convincing path forward for developing successful genetic-based DENV control strategies based on CRISPR/Cas9, which could be expanded to control other arboviruses while maintaining biosafety.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Akbari OS, Matzen KD, Marshall JM, Huang H, Ward CM, Hay BA (2013) A synthetic gene drive system for local, reversible modification and suppression of insect populations. Curr Biol 23:671–677. https://doi.org/10.1016/j.cub.2013.02.059
Akbari OS, Chen CH, Marshall JM, Huang H, Antoshechkin I, Hay BA (2014) Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression. ACS Synth Biol 3(12):915–928. https://doi.org/10.1021/sb300079h
Akbari OS, Bellen HJ, Bier E, Bullock SL, Burt A, Church GM, Cook KR, Duchek P, Edwards OR, Esvelt KM, Gantz VM, Golic KG, Gratz SJ, Harrison MM, Hayes KR, James AA, Kaufman TC, Knoblich J, Malik HS, Matthews KA, O’Connor-Giles KM, Parks AL, Perrimon N, Port F, Russell S, Ueda R, Wildonger J (2015) BIOSAFETY: safeguarding gene drive experiments in the laboratory. Science 349:927–929. https://doi.org/10.1126/science.aac7932
Alphey N, Bonsall MB (2014) Interplay of population genetics and dynamics in the genetic control of mosquitoes. J R Soc Interface 11:20131071. https://doi.org/10.1098/rsif.2013.1071
Alphey L, Beard CB, Billingsley P, Coetzee M, Crisanti A, Curtis C, Eggleston P, Godfray C, Hemingway J, Jacobs-Lorena M, James AA, Kafatos FC, Mukwaya LG, Paton M, Powell JR, Schneider W, Scott TW, Sina B, Sinden R, Sinkins S, Spielman A, Touré Y, Collins FH (2002) Malaria control with genetically manipulated insect vectors. Science 298:119–121. https://doi.org/10.1126/science.1078278
Alphey L, McKemey A, Nimmo D, Neira Oviedo M, Lacroix R, Matzen K, Beech C (2013) Genetic control of Aedes mosquitoes. Pathog Glob Health 107:170–179. https://doi.org/10.1179/2047773213Y.0000000095
Aylon Y, Kupiec M (2004) DSB repair: the yeast paradigm. DNA Repair (Amst) 3:797–815. https://doi.org/10.1016/j.dnarep.2004.04.013
Bassett AR, Tibbit C, Ponting CP, Liu J-L (2013) Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep 4:220–228. https://doi.org/10.1016/j.celrep.2013.06.020
Basu S, Aryan A, Overcash JM, Samuel GH, Anderson MAE, Dahlem TJ, Myles KM, Adelman ZN (2015) Silencing of end-joining repair for efficient site-specific gene insertion after TALEN/CRISPR mutagenesis in Aedes aegypti. Proc Natl Acad Sci 112:4038–4043. https://doi.org/10.1073/pnas.1502370112
Benedict M (2003) The first releases of transgenic mosquitoes: an argument for the sterile insect technique. Trends Parasitol 19:349–355. https://doi.org/10.1016/S1471-4922(03)00144-2
Benedict M, D’Abbs P, Dobson S, Gottlieb M, Harrington L, Higgs S, James A, James S, Knols B, Lavery J, O’Neill S, Scott T, Takken W, Toure Y (2008) Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: recommendations of a scientific working group. Vector-Borne Zoonotic Dis 8:127–166. https://doi.org/10.1089/vbz.2007.0273
Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, Dickman MJ, Makarova KS, Koonin EV, van der Oost J (2008) Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321:960–964. https://doi.org/10.1126/science.1159689
Buchman A, Gamez S, Li M, Antoshechkin I, Li H-H, Wang H-W, Chen C-H, Klein MJ, Duchemin J-B, Crowe JE, Paradkar PN, Akbari OS (2020) Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathog 16:e1008103. https://doi.org/10.1371/journal.ppat.1008103
Burt A (2003) Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc R Soc Lond B Biol Sci 270:921–928. https://doi.org/10.1098/rspb.2002.2319
Burt A (2014) Heritable strategies for controlling insect vectors of disease. Philos Trans R Soc Lond Ser B Biol Sci 369:20130432. https://doi.org/10.1098/rstb.2013.0432
Chen C-H, Huang H, Ward CM, Su JT, Schaeffer LV, Guo M, Hay BA (2007) A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila. Science 316:597–600
Chevalier BS (2001) Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res 29:3757–3774. https://doi.org/10.1093/nar/29.18.3757
Chiruvella KK, Liang Z, Wilson TE (2013) Repair of double-Strand breaks by end joining. Cold Spring Harb Perspect Biol 5:a012757–a012757. https://doi.org/10.1101/cshperspect.a012757
Craig GB, Hickey WA, VandeHey RC (1960) An inherited male-producing factor in Aedes aegypti. Science 132:1887–1889. https://doi.org/10.1126/science.132.3443.1887
Curtis CF (1968) Possible use of translocations to fix desirable genes in insect pest populations. Nature 218:368–369. https://doi.org/10.1038/218368a0
Deredec A, Godfray HCJ, Burt A (2011) Requirements for effective malaria control with homing endonuclease genes. Proc Natl Acad Sci U S A 108:E874–E880. https://doi.org/10.1073/pnas.1110717108
DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM (2015) Safeguarding CRISPR-Cas9 gene drives in yeast. Nat Biotechnol 33:1250–1255. https://doi.org/10.1038/nbt.3412
Dong S, Lin J, Held NL, Clem RJ, Passarelli AL, Franz AWE (2015) Heritable CRISPR/Cas9-mediated genome editing in the yellow fever mosquito, Aedes aegypti. PLoS One 10:e0122353. https://doi.org/10.1371/journal.pone.0122353
Fang J (2010) Ecology: a world without mosquitoes. Nature 466:432–434. https://doi.org/10.1038/466432a
Franz AWE, Sanchez-Vargas I, Piper J, Smith MR, Khoo CCH, James AA, Olson KE (2009) Stability and loss of a virus resistance phenotype over time in transgenic mosquitoes harbouring an antiviral effector gene. Insect Mol Biol 18:661–672. https://doi.org/10.1111/j.1365-2583.2009.00908.x
Fu G, Lees RS, Nimmo D, Aw D, Jin L, Gray P, Berendonk TU, White-Cooper H, Scaife S, Kim Phuc H, Marinotti O, Jasinskiene N, James AA, Alphey L (2010) Female-specific flightless phenotype for mosquito control. Proc Natl Acad Sci 107:4550–4554. https://doi.org/10.1073/pnas.1000251107
Gantz VM, Akbari OS (2018) Gene editing technologies and applications for insects. Curr Opin Insect Sci 28:66–72. https://doi.org/10.1016/j.cois.2018.05.006
Gantz VM, Bier E (2015) Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science 348:442–444. https://doi.org/10.1126/science.aaa5945
Gantz VM, Bier E (2016) The dawn of active genetics. BioEssays 38:50–63. https://doi.org/10.1002/bies.201500102
Garneau JE, Dupuis M-È, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH, Moineau S (2010) The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468:67–71. https://doi.org/10.1038/nature09523
Gasiunas G, Sinkunas T, Siksnys V (2014) Molecular mechanisms of CRISPR-mediated microbial immunity. Cell Mol Life Sci 71:449–465. https://doi.org/10.1007/s00018-013-1438-6
Gould EA, Higgs S (2009) Impact of climate change and other factors on emerging arbovirus diseases. Trans R Soc Trop Med Hyg 103:109–121. https://doi.org/10.1016/j.trstmh.2008.07.025
Grunwald HA, Gantz VM, Poplawski G, Xu X-RS, Bier E, Cooper KL (2019) Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline. Nature 566:105–109. https://doi.org/10.1038/s41586-019-0875-2
Hall AB, Basu S, Jiang X, Qi Y, Timoshevskiy VA, Biedler JK, Sharakhova MV, Elahi R, Anderson MAE, Chen X-G, Sharakhov IV, Adelman ZN, Tu Z (2015) A male-determining factor in the mosquito Aedes aegypti. Science 348:1268–1270. https://doi.org/10.1126/science.aaa2850
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) Europe PMC Funders Group Europe PMC Funders author manuscripts: A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol 34:78–83. https://doi.org/10.1038/nbt.3439
Hartenian E, Doench JG (2015) Genetic screens and functional genomics using CRISPR/Cas9 technology. FEBS J 282:1383–1393. https://doi.org/10.1111/febs.13248
Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734. https://doi.org/10.1038/nbt.1927
Honório NA, Codeço CT, Alves FC, Magalhães MAFM, Lourenço-de-Oliveira R (2009) Temporal distribution of Aedes aegypti in different districts of Rio De Janeiro, Brazil, measured by two types of traps. J Med Entomol 46:1001–1014. https://doi.org/10.1603/033.046.0505
Jackson WT, Giddings TH, Taylor MP, Mulinyawe S, Rabinovitch M, Kopito RR, Kirkegaard K (2005) Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3:e156. https://doi.org/10.1371/journal.pbio.0030156
James AA (2005) Gene drive systems in mosquitoes: rules of the road. Trends Parasitol 21:64–67. https://doi.org/10.1016/j.pt.2004.11.004
Jansen R, van Embden JDA, Wim G, Schouls LM (2002) Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43:1565–1575. https://doi.org/10.1046/j.1365-2958.2002.02839.x
Jasin M, Rothstein R (2013) Repair of strand breaks by homologous recombination. Cold Spring Harb Perspect Biol 5:a012740–a012740. https://doi.org/10.1101/cshperspect.a012740
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821. https://doi.org/10.1126/science.1225829
Juillerat A, Dubois G, Valton J, Thomas S, Stella S, Maréchal A, Langevin S, Benomari N, Bertonati C, Silva GH, Daboussi F, Epinat J-C, Montoya G, Duclert A, Duchateau P (2014) Comprehensive analysis of the specificity of transcription activator-like effector nucleases. Nucleic Acids Res 42:5390–5402. https://doi.org/10.1093/nar/gku155
Kass EM, Jasin M (2010) Collaboration and competition between DNA double-strand break repair pathways. FEBS Lett 584:3703–3708. https://doi.org/10.1016/j.febslet.2010.07.057
Kistler KE, Vosshall LB, Matthews BJ (2015) Genome engineering with CRISPR-Cas9 in the mosquito aedes aegypti. Cell Rep 11:51–60. https://doi.org/10.1016/j.celrep.2015.03.009
Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales APW, Li Z, Peterson RT, Yeh J-RJ, Aryee MJ, Joung JK (2015) Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523:481–485. https://doi.org/10.1038/nature14592
Krueger U, Bergauer T, Kaufmann B, Wolter I, Pilk S, Heider-Fabian M, Kirch S, Artz-Oppitz C, Isselhorst M, Konrad J (2007) Insights into effective RNAi gained from large-scale siRNA validation screening. Oligonucleotides 17:237–250. https://doi.org/10.1089/oli.2006.0065
Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Müller-Lerch F, Fu F, Pearlberg J, Göbel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB, Cathomen T, Voytas DF, Joung JK (2008) Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31:294–301. https://doi.org/10.1016/j.molcel.2008.06.016
Marraffini LA, Sontheimer EJ (2008) CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322:1843–1845. https://doi.org/10.1126/science.1165771
Marshall JM (2009) The effect of gene drive on containment of transgenic mosquitoes. J Theor Biol 258:250–265. https://doi.org/10.1016/j.jtbi.2009.01.031
Otero M, Solari HG, Schweigmann N (2006) A stochastic population dynamics model for Aedes Aegypti: formulation and application to a city with temperate climate. Bull Math Biol 68:1945–1974. https://doi.org/10.1007/s11538-006-9067-y
Porteus M (2016) Genome editing: a new approach to human therapeutics. Annu Rev Pharmacol Toxicol 56:163–190. https://doi.org/10.1146/annurev-pharmtox-010814-124454
Rasgon J (2007) Population replacement strategies for controlling vector populations and the use of Wolbachia pipientis for genetic drive. J Vis Exp:225. https://doi.org/10.3791/225
Reegan AD, Ceasar SA, Paulraj MG, Ignacimuthu S, Al-Dhabi NA (2016) Current status of genome editing in vector mosquitoes: a review. Biosci Trends 10:424–432
Reyon D, Tsai SQ, Khayter C, Foden JA, Sander JD, Joung JK (2012) FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30:460–465. https://doi.org/10.1038/nbt.2170
Rouet P, Smih F, Jasin M (1994) Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol 14:8096–8106. https://doi.org/10.1128/mcb.14.12.8096
Rudin N, Sugarman E, Haber JE (1989) Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae. Genetics 122:519–534
Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh J-RJ, Joung JK (2011a) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8:67–69. https://doi.org/10.1038/nmeth.1542
Sander JD, Yeh J-RJ, Peterson RT, Joung JK (2011b) Engineering zinc finger nucleases for targeted mutagenesis of zebrafish. Methods Cell Biol 104:51–58. https://doi.org/10.1016/B978-0-12-374814-0.00003-3
Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P, Pâques F (2011) Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Curr Gene Ther 11:11–27
Singh RK, Dhama K, Khandia R, Munjal A, Karthik K, Tiwari R, Chakraborty S, Malik YS, Bueno-Marí R (2018) Prevention and control strategies to counter Zika virus, a special focus on intervention approaches against vector mosquitoes—current updates. Front Microbiol 9:87. https://doi.org/10.3389/fmicb.2018.00087
Sinkins SP, Gould F (2006) Gene drive systems for insect disease vectors. Nat Rev Genet 7:427–435. https://doi.org/10.1038/nrg1870
Skipper K, Andersen P, Sharma N, Mikkelsen J (2013) DNA transposon-based gene vehicles—scenes from an evolutionary drive. J Biomed Sci 20:92. https://doi.org/10.1186/1423-0127-20-92
Stoddard BL (2006) Homing endonuclease structure and function. Q Rev Biophys 38:49. https://doi.org/10.1017/S0033583505004063
Touré YT, Oduola AM, Sommerfeld J, Morel CM (2003) Biosafety and risk assessment in the use of genetically modified mosquitoes for disease control. World Health Organization, pp 217–222
van der Oost J, Westra ER, Jackson RN, Wiedenheft B (2014) Unravelling the structural and mechanistic basis of CRISPR–Cas systems. Nat Rev Microbiol 12:479–492. https://doi.org/10.1038/nrmicro3279
von Seidlein L, Kekulé AS, Strickman D (2017) Novel vector control approaches: the future for prevention of Zika virus transmission? PLoS Med 14:e1002219. https://doi.org/10.1371/journal.pmed.1002219
Ward CM, Su JT, Huang Y, Lloyd AL, Gould F, Hay BA (2011) Medea selfish genetic elements as tools for altering traits of wild populations: a theoretical analysis. Evolution 65:1149–1162. https://doi.org/10.1111/j.1558-5646.2010.01186.x
Weaver SC, Reisen WK (2010) Present and future arboviral threats. Antivir Res 85:328–345. https://doi.org/10.1016/j.antiviral.2009.10.008
Windbichler N, Menichelli M, Papathanos PA, Thyme SB, Li H, Ulge UY, Hovde BT, Baker D, Monnat RJ, Burt A, Crisanti A (2011) A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473:212–215. https://doi.org/10.1038/nature09937
World Health Organization (2017) Vector-borne diseases. https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases. Accessed 15 Oct 2020
Wood AJ, Lo T-W, Zeitler B, Pickle CS, Ralston EJ, Lee AH, Amora R, Miller JC, Leung E, Meng X, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Meyer BJ (2011) Targeted genome editing across species using ZFNs and TALENs. Science 333:307. https://doi.org/10.1126/science.1207773
Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, Koonin EV, Zhang F (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759–771. https://doi.org/10.1016/j.cell.2015.09.038
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Wickramasinghe, P.D.S.U., Silva, G.N., Silva Gunawardene, Y.I.N., Dassanayake, R.S. (2021). Advances in Aedes Mosquito Vector Control Strategies Using CRISPR/Cas9. In: Tyagi, B.K. (eds) Genetically Modified and other Innovative Vector Control Technologies. Springer, Singapore. https://doi.org/10.1007/978-981-16-2964-8_4
Download citation
DOI: https://doi.org/10.1007/978-981-16-2964-8_4
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-2963-1
Online ISBN: 978-981-16-2964-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)