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. Author manuscript; available in PMC: 2024 May 2.
Published in final edited form as: Trends Parasitol. 2023 Nov 24;40(1):75–88. doi: 10.1016/j.pt.2023.11.001

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

Figure 1.

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.