Advances and challenges in synthetic biology for mosquito control

Abstract

Mosquito-borne illnesses represent a significant global health peril, resulting in approximately one million fatalities annually. West Nile, dengue, Zika, and malaria are continuously expanding their global reach, driven by factors that escalate mosquito populations and pathogen transmission. Innovative control measures are imperative to combat these catastrophic ailments. Conventional approaches, such as eliminating breeding sites and using insecticides, have been helpful, but they face challenges such as insecticide resistance and environmental harm. Given the mounting severity of mosquito-borne diseases, there is promise in exploring innovative approaches using synthetic biology to bolster mosquitoes' resistance to pathogens, or even eliminate the mosquito vectors, as a means of control. This review outlines current strategies, future goals, and the importance of gene editing for global health defenses against mosquito-borne diseases.

Keywords: gene editing; genetic biocontrol; synthetic biology; vector-borne diseases.

Figure 1.. Synthetic biology-based strategies for mosquito control.

The figure summarizes synthetic mosquito-control strategies. Both pgSIT and Ifegenia use the CRISPR-Cas9 system to target essential genes in mosquitoes. pgSIT targets essential genes in female mosquitoes, aiming either to eliminate them or induce functional lethality, which leads to the removal of female mosquitoes. Also, it targets genes related to sperm development to sterilize males. Ifegenia eliminates female mosquitoes through precise gene targeting [femaless (fle) gene], resulting in populations consisting only of males, thereby leading to effective suppression of the mosquito population. Homing-endonuclease genes (HEGs) have a precise capability to cleave specific nucleotide sequences. When the targeted sequence resides on the X chromosome, and the HEG is active during spermatogenesis, potential outcomes encompass the generation of nonviable female offspring or the selective reduction of X-carrying sperm cells. Once the HEG is inserted into the potential cleavage site, the subsequent repair process, homology-directed repair (HDR), following HEG-induced cleavage can result in the duplication of the allele carrying the HEG, a phenomenon known as ‘homing’. The homing event within the germ line gives rise to an inheritance pattern that exceeds the usual Mendelian ratios, with over 50% of the offspring from an HEG heterozygote inheriting the allele that carries the HEG. REAPER (vRNA expression activates poisonous effector ribonuclease), a CasRx system that specifically targets RNA viral genomes, becomes active in the presence of the targeted arbovirus, such as chikungunya. Consequently, the REAPER approach substantially reduces viral replication, and its precise targeting (virus-induced collateral effect) could potentially result in the mortality of infected mosquitoes. Abbreviations: CRISPR, clustered regularly interspaced short palindromic repeats; gRNA, guide RNA; Ifegenia, Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles; pgSIT, precision-guided sterile insect technique.; vRNA, viral RNA.