Engineered Resistance to Plasmodium falciparum Development in Transgenic Anopheles stephensi

Isaacs, Alison T.; Li, Fengwu; Jasinskiene, Nijole; Chen, Xiaoguang; Nirmala, Xavier; Marinotti, Osvaldo; Vinetz, Joseph M.; James, Anthony A.

doi:10.1371/journal.ppat.1002017

Cited by 126 publications

(135 citation statements)

References 43 publications

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“…These methods are hampered by insecticide resistance and the high maintenance costs required to sustain the measures. The development of genetically modified mosquitoes (GMMs) that are resistant to parasite infection (which aims to reduce and/or block Plasmodium transmission) is being undertaken (James et al 1999, Rodrigues et al 2008, Isaacs et al 2011, although the impact of GMMs in the field must be carefully evaluated prior to widespread use.…”

Section: Malaria Treatment and Drug-resistant Parasites -mentioning

confidence: 99%

New approaches in antimalarial drug discovery and development: a review

Aguiar

Rocha

Souza

et al. 2012

Mem. Inst. Oswaldo Cruz

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Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria

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Section: Malaria Treatment and Drug-resistant Parasites -mentioning

confidence: 99%

New approaches in antimalarial drug discovery and development: a review

Aguiar

Rocha

Souza

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…As such, many transgenic lines are actually populations of mosquitoes consisting of individuals with different qualitative and quantitative transgene representations generated by insertion-site effects, linkage, independent assortment, and hemi-or homozygosity. These differences may account for some of the variation in the phenotypes of many of the transgenes reported in the literature (51,52) and for the observed variation in the biological replicates done here. These data support a hypothesis that the major qualitative and quantitative effects of a transgene result likely from only one of the multiple insertions.…”

Section: Discussionmentioning

confidence: 76%

Exogenous gypsy insulator sequences modulate transgene expression in the malaria vector mosquito, Anopheles stephensi

Carballar-Lejarazú

Jasinskiene

James

2013

Proc. Natl. Acad. Sci. U.S.A.

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Malaria parasites are transmitted to humans by mosquitoes of the genus Anopheles, and these insects are the targets of innovative vector control programs. Proposed approaches include the use of genetic strategies based on transgenic mosquitoes to suppress or modify vector populations. Although substantial advances have been made in engineering resistant mosquito strains, limited efforts have been made in refining mosquito transgene expression, in particular attenuating the effects of insertions sites, which can result in variations in phenotypes and impacts on fitness due to the random integration of transposon constructs. A promising strategy to mitigate position effects is the identification of insulator or boundary DNA elements that could be used to isolate transgenes from the effects of their genomic environment. We applied quantitative approaches that show that exogenous insulator-like DNA derived from the Drosophila melanogaster gypsy retrotransposon can increase and stabilize transgene expression in transposon-mediated random insertions and recombinase-catalyzed, site-specific integrations in the malaria vector mosquito, Anopheles stephensi. These sequences can contribute to precise expression of transgenes in mosquitoes engineered for both basic and applied goals.transgenesis | transposase

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“…Several other researchers have followed this strategy and developed transgenic mosquitoes that cannot transmit their parasites. Bee venom phospholipases, synthetic antimalaria proteins like vida3, single chain antibodies (scFv) targeting malaria parasites, as well as an antimicrobial peptide cecropin A have been used as effectors and mosquitoes engineered to express them lack the ability to effectively transmit parasites [52][53][54][55][56]. RNAi-based resistance to dengue virus has also been engineered in Ae.…”

Section: Mosquitoesmentioning

confidence: 99%

Developing the Arsenal Against Pest and Vector Dipterans: Inputs of Transgenic and Paratransgenic Biotechnologies

Ogaugwu¹,

Durvasula²

2017

Biological Control of Pest and Vector Insects

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Insects are the most numerous of all animals and are found in almost every inhabitable place on earth. The order Diptera (true flies) contains many members that are notorious agricultural pests, nuisance or vectors of diseases. The list is long: mosquitoes, tsetse flies, screw worms, fruit flies, sand flies, blow flies, house flies, gall and biting midges, black flies, leaf miners, horse flies, and so on. Efforts to combat some of these pests and vectors have resulted in control measures such as the chemical, physical, and cultural control methods. These methods, though largely beneficial, have disadvantages and limitations, which sometimes seem to outweigh the problems initially sought to be controlled. The chemical method, for example, is not environment-friendly since it negatively affects many nontarget organisms and disrupts ecosystem balance. Development of insecticide resistance by pests/vectors is another concern. Molecular biotechnology has introduced vast arrays of novel ways to tackle pests and disease vectors, as well as improve the potency of existing control methods. This chapter looks at transgenic and paratransgenic biotechnologies and how they have been applied so far to develop and expand the arsenal against dipteran pests and disease vectors. Further, we discuss the advantages, disadvantages, and limitations of these technologies.

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Engineered Resistance to Plasmodium falciparum Development in Transgenic Anopheles stephensi

Cited by 126 publications

References 43 publications

New approaches in antimalarial drug discovery and development: a review

New approaches in antimalarial drug discovery and development: a review

Exogenous gypsy insulator sequences modulate transgene expression in the malaria vector mosquito, Anopheles stephensi

Developing the Arsenal Against Pest and Vector Dipterans: Inputs of Transgenic and Paratransgenic Biotechnologies

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