the scienceSignificance
Novel genetic strategies for the malaria eradication agenda exploit Cas9/gRNA (guide RNA)-based autonomous gene-drive systems carrying antiparasite effector genes, and these effectively reduce prevalence and numbers of the human parasite, Plasmodium falciparum, in the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii. Results from laboratory assessments of population gene-drive dynamics, transgene genetic loads, and parasite suppression efficacy informed modeling of conceptual field releases that show that hypothetical strains based on the empirical data could have a meaningful epidemiological impact in reducing human incidence by 50 to 90%.
Abstract
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)–based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
the UNthe other opinionImagine genetically engineered mosquitoes designed to inherit their genes to all offspring, jeopardise the food chain, and wipe out their natural siblings by making them infertile. [1]
According to scientists there is a risk that the so called gene drive could even spread from mosquitoes to butterflies, killing pollinators in masses, risking crops, plants and entire ecosystems. [2]
Nobody pushing the new technology has a solution to mitigate those risks, but even so there are plans in action to make this a reality. Most of the funding to make this happen is being provided by the US military and the Bill and Melinda Gates Foundation.
In the lead up to the key UN meeting in 2021, there will be important decisions taken at expert conferences. The EU is represented at all these conferences. The European Parliament has already requested for the EU Commission and its Member States to call for a global moratorium on the environmental release of gene drive organisms. But that is not enough: our voices can make all the difference.
Malaria in AfricaNearly every minute, a child under five dies of malaria. Many of these deaths are preventable and treatable. In 2021, there were 247 million malaria cases globally that led to 619,000 deaths in total. Of these deaths, 77 per cent were children under 5 years of age. This translates into a daily toll of over one thousand children under age 5.
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