Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial...

Area of Science:

• Genetics and Genomics
• Vector Biology
• Population Dynamics

Background:

• Homing gene drives targeting Anopheles gambiae, the primary malaria vector, have been developed to disrupt female fertility and induce population collapse.
• CRISPR/Cas9-based gene drives, including those utilizing specific promoters like zpg and nos, are being investigated as novel malaria control strategies.
• An X-shredder element was incorporated into a gene drive to bias inheritance towards male offspring, potentially enhancing population suppression.

Purpose of the Study:

• To analyze experimental data of two Anopheles gambiae homing gene drives (one zpg-promoter based, one combined zpg/X-shredder) to characterize their performance.
• To compare the experimental performance of these gene drives with previous interpretations using an individual-based simulation framework.
• To assess the effectiveness of gene drives in suppressing mosquito populations in a spatially continuous model.

Main Methods:

• Analysis of experimental data from two distinct Anopheles gambiae homing gene drives.
• Development and application of an individual-based simulation framework to model mosquito population dynamics in continuous space.
• Comparison of simulation results with previous interpretations of gene drive experimental performance.

Main Results:

• The zpg-promoter based homing drive successfully eliminated a laboratory cage population of mosquitoes.
• The combined homing/X-shredder drive demonstrated reduced effectiveness in population suppression within the simulation model, often failing to achieve complete collapse.
• The combined drive frequently resulted in an unstable equilibrium between drive and wild-type alleles, rather than complete population suppression.

Conclusions:

• Contrary to expectations, the combined homing/X-shredder drive was less effective for population suppression than the zpg-promoter drive alone in the modeled context.
• Gene drives based on the nos promoter, despite similarities, may represent more promising candidates for future malaria vector control development.
• Further modeling and experimental validation are crucial for optimizing gene drive strategies for effective Anopheles gambiae population suppression.