Dominant resistance alleles accelerate population suppression by CRISPR-based gene drive

CRISPR-based gene drive is a promising strategy for pest control. However, when targeting a recessive fertility gene, nonfunctional resistance alleles generated by end-joining slow the spread of drive and can even impair suppressive power. It was recently discovered that a doublesex target site can result in dominant female-sterile alleles when disrupted. It could serve as an ideal target for suppression drives, as disrupted alleles are efficiently removed when inherited by a female, increasing the suppressive power of the drive. Here, to better understand how dominant sterile target sites can improve suppression, we used an individual-based, continuous space model to investigate chasing dynamics of homing drives that produce dominant female-sterile resistance. Our results indicate that dominant-sterile resistance allows homing drives to achieve higher population elimination rates and a lower probability of chasing over a broader range of performance parameters. In addition, we propose a confined gene drive system, termed TADFI (Toxin-Antidote Dominant Female Intersex), that is also based on formation of dominant female sterile alleles. TADFI has two variants, designed for population suppression and modification, respectively. We estimate the introduction frequency threshold of TADFI in a panmictic model, and evaluate its suppression dynamics in a spatial model. Though spreading less rapidly than Toxin-Antidote Dominant Embryo (TADE) suppression drive, it has similar favorable dynamics related to confinement and suppressive power, while potentially being easier to construct. Together these results show that drives generating dominant-female sterile alleles may be promising candidates for a variety of population suppression applications.