Gene drive-based population suppression in the malaria vector Anopheles stephensi

Area of Science:

• Genetics
• Entomology
• Vector Control

Background:

• Gene drives offer novel strategies for pest control by altering inheritance patterns.
• Anopheles stephensi is a primary vector for urban malaria transmission.

Purpose of the Study:

• To construct and evaluate a homing suppression gene drive targeting Anopheles stephensi.
• To assess the drive's efficacy, fitness effects, and potential for resistance.
• To explore combinations for enhanced drive performance.

Main Methods:

• Construction of a homing suppression gene drive targeting the doublesex gene in Anopheles stephensi.
• Incorporation of two gRNAs and a nanos-Cas9 for reduced resistance and improved fitness.
• Evaluation of drive conversion rates, sterility, and intersex phenotypes in homozygotes and heterozygotes.
• Amplicon sequencing to detect resistance allele formation.
• Combination with a vasa-Cas9 line to assess boosted conversion rates.

Main Results:

• The gene drive induced recessive sterility in both male and female Anopheles stephensi homozygotes, with intersex phenotypes observed.
• Drive heterozygotes exhibited moderate conversion rates, suggesting lower nanos promoter activity in this species.
• Resistance allele formation was detected at very low levels.
• Combining the homing drive with a vasa-Cas9 line resulted in 100% drive conversion.

Conclusions:

• The developed gene drive shows potential for Anopheles stephensi population suppression.
• The combination strategy significantly enhances drive conversion efficiency.
• This approach could lead to more effective and environmentally friendly disease vector control methods.