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Transgenic mosquitoes
The document discusses transgenic mosquitoes, which are genetically modified organisms used to interrupt the transmission of vector-borne diseases like dengue, zika, and malaria. It covers various methods of modification, including using dominant lethal genes, the sterile insect technique, and artificial infections, highlighting their potential benefits and drawbacks. Despite the promise they hold, periodic releases of transgenic mosquitoes may incur significant costs and the development of resistance remains a concern.
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Transgenic mosquitoes
- 1. Genetic Modified Organisms : TransgenicMosquitoes Presented by:Presented by: ANIL KUMARANIL KUMAR M.Sc. PHE iiM.Sc. PHE iindnd SemSem 2015-172015-17 VCRC(ICMR)VCRC(ICMR)
- 2. Your company slogan Terminologies TransgeneTransgene:: Gene orgenetic material from one source added to otherGene orgenetic material from one source added to other organism.organism. Transgenesis :Transgenesis : the process of introducing an exogenous gene (transgene) into athe process of introducing an exogenous gene (transgene) into a living organism so that the organism will exhibit a new propertyliving organism so that the organism will exhibit a new property and transmit that property to its offspringand transmit that property to its offspring.. Genetically modified Organisms :Genetically modified Organisms : Organisms (i.e. plants , animals ormicroorganisms) in which theOrganisms (i.e. plants , animals ormicroorganisms) in which the genetic material (DNA) has been altered in a way that does notgenetic material (DNA) has been altered in a way that does not occurnaturally by mating and/ornatural recombination.occurnaturally by mating and/ornatural recombination.
- 3. Your company slogan Continued… TransgenicMosquitoes :Transgenic Mosquitoes : Mosquitoes in which genetic material (DNA) has been altered in aMosquitoes in which genetic material (DNA) has been altered in a way that does not occurnaturally by mating and/ornaturalway that does not occurnaturally by mating and/ornatural recombination.recombination. It is used in interruption of VectorBorne Disease (VBD) cycle.It is used in interruption of VectorBorne Disease (VBD) cycle.
- 4. Your company slogan Need??? Inspite of more than 70 years of vectorcontrolInspite of more than 70 years of vectorcontrol operations disease burden is still persisting.operations disease burden is still persisting. Development of resistance against Chemicals usedDevelopment of resistance against Chemicals used in vectorcontrol operations.in vectorcontrol operations. Environment and health hazards related to ChemicalEnvironment and health hazards related to Chemical control of mosquito vectors.control of mosquito vectors. Biological methods are not much effective.Biological methods are not much effective.
- 5. Your company slogan Tableof Contents 2. Methods2. Methods 3. Role in vector control3. Role in vector control 4. Drawbacks4. Drawbacks 1. Introduction1. Introduction
- 6. Your company slogan Introduction Formore than two decades, scientists have beenFormore than two decades, scientists have been working to develop genetically modified mosquitoesworking to develop genetically modified mosquitoes foruse as public health tools to prevent theforuse as public health tools to prevent the transmission of mosquito borne diseases.transmission of mosquito borne diseases. Recent advances in the development of geneticallyRecent advances in the development of genetically modified mosquitoes have raised hopes forthemodified mosquitoes have raised hopes forthe availability of new, potent and cost-effective tools toavailability of new, potent and cost-effective tools to aid in the fight against Dengue, Zika and malaria.aid in the fight against Dengue, Zika and malaria. Initial lab trails and small scale field trials haveInitial lab trails and small scale field trials have shown a good result inshown a good result in AedesAedes aegyptiaegypti andand Ano phelesAno pheles ablimanuablimanuss control.control.
- 7. FIRST RELEASE OFTRANSGENIC MOSQUITOES
- 8. Your company slogan Strategiesby transgenic mosquitoes PopulationPopulation REPLACEMENTREPLACEMENT PopulationPopulation suppressionsuppression TransgenicTransgenic mosquitoesmosquitoes
- 9. Your company slogan SELF–SELF – PERSISTINGPERSISTING Self - limitingSelf - limiting Transgenic mosquitoes Population Population suppression suppression Po pulatio n Po pulatio n REPLAC EM EN T REPLAC EM EN T
- 10. Your company slogan NATURALALLELE SELF-LIMITING PERSISTENSE SELF-PERSISTAINING INVASIVENESS Types of transgenesis in mosquitoesTypes of transgenesis in mosquitoes
- 11. Your company slogan Sterileinsect technique The most strongly self-sustaining strategies involeThe most strongly self-sustaining strategies invole the use of sterile insects.the use of sterile insects. Mostly sterile-male strategies involve the use ofMostly sterile-male strategies involve the use of heritable lethal genes ormutations.heritable lethal genes ormutations. Fully penetrant sterile/lethal traits the modificationFully penetrant sterile/lethal traits the modification is strongly self-limiting ,as it disappears within ais strongly self-limiting ,as it disappears within a generation unless additional modified insects aregeneration unless additional modified insects are released.released. Irradiation, chemosterilization, transgenicIrradiation, chemosterilization, transgenic sterilization were the ancient methods of malesterilization were the ancient methods of male sterilization.sterilization. Mosquitoes are modified by adding a gene thatMosquitoes are modified by adding a gene that produces a protein called tetracycline repressibleproduces a protein called tetracycline repressible activatorvariant tTAV.activatorvariant tTAV.
- 12. Your company slogan Continued…. tTAV can able to act as a SWITCHthat controls thetTAV can able to act as a SWITCHthat controls the activity of othergenesactivity of othergenes GMmosquito produces higheramount of this tTAVGMmosquito produces higheramount of this tTAV proteinprotein As it activates its own gene, this will ties up some ofAs it activates its own gene, this will ties up some of the cell machinery.the cell machinery. The modified gene is actually a lethal gene.The modified gene is actually a lethal gene. Tetracycline acts as an antidot to this gene.Tetracycline acts as an antidot to this gene. Hence the mosquitoes are supplimented withHence the mosquitoes are supplimented with tetracycline and mate with the wild mosquitoes.tetracycline and mate with the wild mosquitoes. The offsprings inherit the lethal gene and due to theThe offsprings inherit the lethal gene and due to the insufficiency of tetracycline in the field they will die.insufficiency of tetracycline in the field they will die.
- 13. Your company slogan RIDL Release of insects carrying a dominant lethal geneticRelease of insects carrying a dominant lethal genetic system (RIDL)system (RIDL) Two types :-Two types :- fsRIDL (femalespecific RIDL) bi-sex RIDL It uses a lethal gene expressed in the zygot, ratherIt uses a lethal gene expressed in the zygot, rather than in the paternal parent.than in the paternal parent. It releases transgenic mosquito homozygous fortheIt releases transgenic mosquito homozygous forthe repressible dominant lethal gene.repressible dominant lethal gene. In fsRIDL the lethal gene is female specific;In fsRIDL the lethal gene is female specific; Femaleoffspringswill die Heterozygousmaleoffsprigswill bealive If theseheterozygousmalesmatehalf of their offspring inherit the femalelethal transgene
- 14. Your company slogan Continued Inbi-sex RIDLthe heterozygous offspringsIn bi-sex RIDLthe heterozygous offsprings are killed by the inherited lethal gene.are killed by the inherited lethal gene.
- 15. Your company slogan IncompatibleInsect Technique (IIT) WolbachiaWolbachiainfected males were successfully used forinfected males were successfully used for vectorcontrol.vectorcontrol. Sterility can also be created by artificial infectionSterility can also be created by artificial infection with various strains ofwith various strains of Wolbachia.Wolbachia. WolbachiaWolbachiain effects conducts a sterile-male attack inin effects conducts a sterile-male attack in uninfected females.uninfected females. ForFor Wolbachia,Wolbachia, all embryos produced by an infectedall embryos produced by an infected motherare infected.motherare infected. In addition, embryos are nonviable if fertilized by aIn addition, embryos are nonviable if fertilized by a male carrying amale carrying a WolbachiaWolbachiastrain not carried by thestrain not carried by the femalefemale
- 16. Your company slogan HomingEndonuclease Gene HEGs are selfish DNA elements encoding proteinsHEGs are selfish DNA elements encoding proteins (endonucleases) that recognise and cleave specific(endonucleases) that recognise and cleave specific DNA sequences of ˜20-30 nucleotides.DNA sequences of ˜20-30 nucleotides. HEGs may drive recessive lethal orsterile alleles toHEGs may drive recessive lethal orsterile alleles to the population, potentially forcing it to extinction.the population, potentially forcing it to extinction. Homing :- when the HEG is inserted into theHoming :- when the HEG is inserted into the potential site, repairof the HEG induced cut can copypotential site, repairof the HEG induced cut can copy the HEG-bearing allele.the HEG-bearing allele. Occurrence of homing in the germ line causes super-Occurrence of homing in the germ line causes super- Mendelian inheritence, whereby more than 50% ofMendelian inheritence, whereby more than 50% of the offspring of a HEG heterozygote carry the HEG.the offspring of a HEG heterozygote carry the HEG. It is of two types :-It is of two types :- X-shredder Sterileallele
- 17. Your company slogan Continued… If the HEGs cut X-linked sequence and the HEG isIf the HEGs cut X-linked sequence and the HEG is expressed during spermatogenesis, this may resultsexpressed during spermatogenesis, this may results inin Nonviabledaughters Theelimination of X-bearing system If the X-shredderis Y-linked, all male offspringsIf the X-shredderis Y-linked, all male offsprings carry it, which can lead to invasion through meioticcarry it, which can lead to invasion through meiotic drivedrive
- 18. Your company slogan Transmissionblocking vaccines It consist of antibodies that are ingested by theIt consist of antibodies that are ingested by the mosquito with the blood meal and interfere withmosquito with the blood meal and interfere with parasite development.parasite development. Proteins expressed on the surface of gametes ofProteins expressed on the surface of gametes of parasites (eg., Pfs47/Pfs230) and ookinetes (eg.,parasites (eg., Pfs47/Pfs230) and ookinetes (eg., Pfs25 &Pfs28) have been tested forsuch vaccines.Pfs25 &Pfs28) have been tested forsuch vaccines. Antibodies against these protein bind to the parasiteAntibodies against these protein bind to the parasite and block ookinete invasion of the midgutand block ookinete invasion of the midgut epithelium.epithelium. Mosquito midgut antigens could be targeted.Mosquito midgut antigens could be targeted.
- 19. Your company slogan Paratransgenesis It is the genetic manipulation of commensal orsymbioticIt is the genetic manipulation of commensal orsymbiotic bacteria to alterthe host’s ability to transmit a pathogenbacteria to alterthe host’s ability to transmit a pathogen It is an alternative means of preventing malariaIt is an alternative means of preventing malaria transmissiontransmission Bacteria can be engineered to express and secreteBacteria can be engineered to express and secrete peptides orproteins that block parasite invasion orkillpeptides orproteins that block parasite invasion orkill the parasite in the midgutthe parasite in the midgut Gram-positive and gram negative bacteria includingGram-positive and gram negative bacteria including Escherichia, Alcaligenes, Pseudomonas, SerratiaandEscherichia, Alcaligenes, Pseudomonas, Serratiaand BacillusBacillus have been identified in the midgut of wildhave been identified in the midgut of wild mosquitomosquito Eg.,Eg., An. stephensiAn. stephensi fed withfed with E. ColiE. Coli that express a fusionthat express a fusion protein of ricin and single chain antibody againstprotein of ricin and single chain antibody against P.P. BergheiBerghei ookinete surface protein and inhibited the oocystookinete surface protein and inhibited the oocyst
- 20. Your company slogan Promotersand Effectorgenes To produce GMculicine mosquitoes and AnophelineTo produce GMculicine mosquitoes and Anopheline mosquitoes which interfere withmosquitoes which interfere with PlasmodiumPlasmodium development promoters and effectorgenes can be useddevelopment promoters and effectorgenes can be used Effectergenes products are those which hindertheEffectergenes products are those which hinderthe parasite development.parasite development. Promoters are those which drive the transgenesPromoters are those which drive the transgenes Single chain antibodies that recognize surface proteinsSingle chain antibodies that recognize surface proteins show promise in interfering with parasite developmentshow promise in interfering with parasite development An anti-Pbs21 single chain antibody inhibited oocystAn anti-Pbs21 single chain antibody inhibited oocyst formation by upto 95%formation by upto 95% A single chain antibody againstA single chain antibody against P. gallinaceumP. gallinaceum Circunsporozoite protein(CSP), expressed from a SinbdisCircunsporozoite protein(CSP), expressed from a Sinbdis virus vector, reduced numberof parasite in the salivaryvirus vector, reduced numberof parasite in the salivary glands by 99%glands by 99%
- 21. Your company slogan Continued… Transgenic mosquitoes expressing bee venom PLA2Transgenic mosquitoes expressing bee venom PLA2 from the carboxypeptidase promoterreducedfrom the carboxypeptidase promoterreduced P.P. bergheiberghei oocyst formation by 87%.oocyst formation by 87%. TransgenicTransgenic An. stephensiAn. stephensi expressing PLA2 fromexpressing PLA2 from AgAper1 promoterinhibited oocyst formation.AgAper1 promoterinhibited oocyst formation. An alternative strategy is to use synthetic moleculesAn alternative strategy is to use synthetic molecules to interfere with parasite development.to interfere with parasite development. An. stephensiAn. stephensi engineered with a synthetic geneengineered with a synthetic gene expressing a SM1 tetramerunderthe control of theexpressing a SM1 tetramerunderthe control of the carboxypeptidase promoterreduced thecarboxypeptidase promoterreduced the P.P. bbegheieghei development.development.
- 22. Your company slogan Refractorygenes These are genes that conferring the ability toThese are genes that conferring the ability to transmit the pathogen orparasitetransmit the pathogen orparasite Refractory genes may be used where modestRefractory genes may be used where modest prevalence and duration are adequateprevalence and duration are adequate It can be used with a self-limiting driversystem eg.,It can be used with a self-limiting driversystem eg., Killer-rescueKiller-rescue Orwithout a driversystem eg., Multi locusOrwithout a driversystem eg., Multi locus assortment(MLA)assortment(MLA) Dissociation of refractory gene:- loss of refractoryDissociation of refractory gene:- loss of refractory gene DNA from a gene drive construct such that thegene DNA from a gene drive construct such that the refractory gene no longerfunctionsrefractory gene no longerfunctions
- 23. Your company slogan GeneDrive Systems forSpreading Refractory Genes Using Transposible elements (Tes)Using Transposible elements (Tes) One of the first gene drive systems to gainOne of the first gene drive systems to gain widespread attentionwidespread attention TEs replicate within a host genome and hence areTEs replicate within a host genome and hence are inherited more frequently in offspring’s genomeinherited more frequently in offspring’s genome The increase in inheritance enables TEs to spreadThe increase in inheritance enables TEs to spread even in the presence of fitness cost to the hosteven in the presence of fitness cost to the host This has lead to widespread prevalence among manyThis has lead to widespread prevalence among many taxataxa Various families of TEs represent 47% of theVarious families of TEs represent 47% of the AedesAedes aegyptiaegypti mosquito genomemosquito genome
- 24. Your company slogan Medeaelements Maternal effect dominant embryonic arrest is aMaternal effect dominant embryonic arrest is a selfish gene composed of a toxin and an antidoteselfish gene composed of a toxin and an antidote A mothercarrying Medea will express the toxin inA mothercarrying Medea will express the toxin in hergermline and kill herprogenyhergermline and kill herprogeny The offspring with medea allele produce copies ofThe offspring with medea allele produce copies of the antidote that saving theirlivesthe antidote that saving theirlives In a heterozygous motherwith one medea alleleIn a heterozygous motherwith one medea allele and one non-medea allele,and one non-medea allele, half of theoffspringswill inherit themedeaalleleand survive Other half will inherit thenon-medeaand die
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- 27. Your company slogan drawbacksdrawbacks Self –limiting factor of transgenic mosquitoes will lead to periodic releaseof transgenic mosquitoes. Periodic releaseof transgenic mosquitoeswill beacostlier affair . The SMT requires a very large number of males i.e, 5 sterile males to 1 wild femaleto mate. Invasive genetic system requires more (wolbachia or UD) modified mosquitoesfor their intial establishment. About 3-4% of Sterile Modified Mosquito (SMM) carrying a dominant lethal gene escapes its activation. (Source: Department of Biosafety, Ministry of Natural Resources& Environment of Malaysia) Useof antibioticsin GMM can lead to drug resistance.
- 28. Your company slogan Selection of transgenic mosquitoes is a manual work.Selection of transgenic mosquitoes is a manual work. Selection of transgenic male and female larvae orSelection of transgenic male and female larvae or pupae is manual work.pupae is manual work. Mosquito fitness is a majorconcern.Mosquito fitness is a majorconcern. Immigration into otherareas.Immigration into otherareas. Community involvement, social and ethical issues.Community involvement, social and ethical issues.
- 29. Your company slogan DARKSIDE OF COIN
- 30. Your company slogan OFFTHE RECORDS…. (Coincidene Or .........!!) OX513A was the name given to the modified male mosquitoes that were released in Brazil. They were bred in a lab in the UK and modified to require tetracycline, an antibiotic, to stay alive and destined to dieif they didn’t get aregular supply of it. Oxitech did two trialsin Brazil i.e, 2012 and 2015. Zika is not new to world, it was discovered in Uganda in 1947, microcephaly is a complication of zika which was first reported from the same area of Brazil whereOxitech did it trials. Colombia, a neighbour of Brazil has recorded more than 20,000 cases of zika but has only reported a small increase of microcephaly related to zika. (up to April 16th 2016)
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- 32. Your company slogan QUESTIONSYETTO BEANSWERED...!! Are we prepared for any epidemics because of gmm? Are we prepared against gmm, if it is used as bioterrorism weapon? Ecological niche created by wiping a mosquito species will be filled by other species so can gmm be used as only option? If we are wiping a mosquito species from an area it may lead to infiltration on the mosquitoes from the neighboring areas, so release of gmm will it be a continuous process? if you are releasing gmm (Aedes aegypti) in an area and in the same place any epidemic occurs because of other vector what control measures one will take ?? 15 % of transgenic mosquitoes escapes the activation of lethal genes as tetracyclin (antidote) is also widely used in the field of agriculture , so if these mosquitoes will bite human then?? It may lead to resistance in mosquitoes too!!