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Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles

The malaria parasite’s complex journey through the Anopheles mosquito vector provides multiple opportunities for targeting Plasmodium with recombinant effectors at different developmental stages and different host tissues. We have designed and expressed transgenes that efficiently suppress Plasmodiu...

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Detalles Bibliográficos
Autores principales: Dong, Yuemei, Simões, Maria L., Dimopoulos, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220273/
https://www.ncbi.nlm.nih.gov/pubmed/32426491
http://dx.doi.org/10.1126/sciadv.aay5898
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author Dong, Yuemei
Simões, Maria L.
Dimopoulos, George
author_facet Dong, Yuemei
Simões, Maria L.
Dimopoulos, George
author_sort Dong, Yuemei
collection PubMed
description The malaria parasite’s complex journey through the Anopheles mosquito vector provides multiple opportunities for targeting Plasmodium with recombinant effectors at different developmental stages and different host tissues. We have designed and expressed transgenes that efficiently suppress Plasmodium infection by targeting the parasite with multiple independent endogenous and exogenous effectors at multiple infection stages to potentiate suppression and minimize the probability for development of resistance to develop. We have also addressed the fitness impact of transgene expression on the mosquito. We show that highly potent suppression can be achieved by targeting both pre-oocyst stages by transgenically overexpressing either the endogenous immune deficiency immune pathway transcription factor Rel2 or a polycistronic mRNA encoding multiple antiparasitic effectors and simultaneously targeting the sporozoite stages with an anti-sporozoite single-chain antibody fused to the antiparasitic protein Scorpine. Expression of the selected endogenous effector systems appears to pose a lower fitness cost than does the use of foreign genes.
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spelling pubmed-72202732020-05-18 Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles Dong, Yuemei Simões, Maria L. Dimopoulos, George Sci Adv Research Articles The malaria parasite’s complex journey through the Anopheles mosquito vector provides multiple opportunities for targeting Plasmodium with recombinant effectors at different developmental stages and different host tissues. We have designed and expressed transgenes that efficiently suppress Plasmodium infection by targeting the parasite with multiple independent endogenous and exogenous effectors at multiple infection stages to potentiate suppression and minimize the probability for development of resistance to develop. We have also addressed the fitness impact of transgene expression on the mosquito. We show that highly potent suppression can be achieved by targeting both pre-oocyst stages by transgenically overexpressing either the endogenous immune deficiency immune pathway transcription factor Rel2 or a polycistronic mRNA encoding multiple antiparasitic effectors and simultaneously targeting the sporozoite stages with an anti-sporozoite single-chain antibody fused to the antiparasitic protein Scorpine. Expression of the selected endogenous effector systems appears to pose a lower fitness cost than does the use of foreign genes. American Association for the Advancement of Science 2020-05-13 /pmc/articles/PMC7220273/ /pubmed/32426491 http://dx.doi.org/10.1126/sciadv.aay5898 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Dong, Yuemei
Simões, Maria L.
Dimopoulos, George
Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title_full Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title_fullStr Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title_full_unstemmed Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title_short Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles
title_sort versatile transgenic multistage effector-gene combinations for plasmodium falciparum suppression in anopheles
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220273/
https://www.ncbi.nlm.nih.gov/pubmed/32426491
http://dx.doi.org/10.1126/sciadv.aay5898
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