Title: Genetically modified mosquitoes using CRISPR-Cas9 gene editing technology to inhibit the transmission of the malaria parasite
Abstract:
About a quarter billion people are infected with malaria each year, with most cases occurring in sub-Saharan Africa, with a mortality rate of more than 600,000 humans per year. One of the main problems is the superior capacity of the mosquito vectors Anopheles gambiae to acquire and transmit the malaria parasite. With the lack of any potent vaccine, and the spread of drug resistance against the last resort drugs, Artemisinin and Artemisinin combination therapies, approaches that target the mosquito vector are mostly preferred and are showing promising results. One of the most efficient methods that has been recently shown to be highly effective in targeting large population of mosquitoes over large areas is the introduction of the gene drive system. In this study, we are utilizing the CRISPR-Cas9 gene editing technology, to develop a gene-drive (GD) system targeting the dispensable cardinal AgCD and the redundant AgEATER genes for deletion, while simultaneously introducing cassettes of gene encoding the anti-plasmodial effector peptides, MP2 and EPIP under the control of the Lipophorin gene expression elements. Targeting AgCD has proven to produce homozygous males and females easily with no fitness cost and with fertilization competitiveness that outperform WT mosquitoes, which are minimal conditions for a successful gene drive. We will confirm the integration of the knockout constructs carrying the transgene elements and we will also confirm the secretion of Anti-plasmodial peptides in the hemolymph of mosquitoes. This can present an ideal gene drive with further superior anti-plasmodial capacity that could spread in natural mosquito populations to significantly reduce or eliminate malaria burden over large area of land.
Audience Take Away Notes:
- The audience will gain knowledge about the application of CRISPR-Cas9 gene editing technology in developing a gene-drive system targeting mosquito vectors to inhibit the transmission of the Plasmodium parasite, and the potential impact of this system in significantly reducing or eliminating malaria transmission over large areas
- This research relies on a relatively new approach to addressing a public health problem, and hence the knowledge presented in this paper can be expanded on by incorporating CRISPR-based gene editing and gene-drive technologies into their curriculum to educate students about novel approaches in vector biology and disease control
- The proposed solution is practical in that, it offers a novel approach to mosquito control that could simplify and enhance current strategies for malaria prevention and elimination
