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Assessing target genes for homing suppression gene drive
Xuejiao Xu1, Jialing Fang2, Jingheng Chen2
1Center for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking University, Beijing, 100871, China. xuejiao.xu@pku.edu.cn.
The EMBO Journal
|February 6, 2026
Summary
Gene drives targeting female fertility genes in fruit flies show promise for population control. Drives targeting octopamine receptor and stall genes achieved high efficiency, with one successfully suppressing a caged population.
Area of Science:
- Genetics
- Population Biology
- Molecular Biology
Background:
- Gene drives offer a powerful tool for altering wild populations by biasing inheritance.
- Targeting female fertility genes is a strategic approach for population suppression gene drives.
- CRISPR-based homing gene drives provide a precise mechanism for gene drive implementation.
Purpose of the Study:
- To investigate the efficacy of CRISPR-based homing gene drives targeting nine female fertility genes in Drosophila melanogaster for population suppression.
- To assess drive-conversion efficiency and minimize fitness costs in female drive carriers using multiplexed gRNA strategies.
- To evaluate the population suppression potential of promising gene drives in cage experiments.
Main Methods:
- Utilized CRISPR-based homing gene drives targeting nine female fertility genes in Drosophila melanogaster.
- Employed a multiplexed gRNA approach to prevent resistance allele formation.
- Assessed drive efficiency in individual crosses and conducted cage experiments for population suppression trials.
- Investigated fitness costs associated with gene drive carriers, including maternal Cas9 effects.
Main Results:
- Drive-conversion efficiency varied across the nine targeted fertility genes.
- Drives targeting the octopamine β2 receptor (oct) and stall (stl) genes showed the highest conversion rates.
- A stl-targeting drive successfully suppressed a caged population at high release frequency, but failed at lower frequency.
- Observed fitness costs in female drive carriers, partly attributed to maternal Cas9 deposition, impacting suppression efficiency.
Conclusions:
- Octopamine receptor and stall genes are identified as promising targets for fertility-based population suppression gene drives.
- Demonstrated the potential and limitations of fertility-based suppression drives, highlighting the importance of release frequency and fitness costs.
- Findings provide empirical data to inform the design and assessment of more effective gene drive strategies for population control.
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