Figure 1. Existing alteration-type CRISPR gene drive systems should invade well-mixed wild populations.

(A) Typical construction and function of alteration-type CRISPR gene drive systems. A drive construct (D), including a CRISPR nuclease, guide RNA (gRNA), and ‘cargo’ sequence, induces cutting at a wild-type allele (W) with homology to sequences flanking the drive construct. Repair by homologous recombination (HR) results in conversion of the wild-type to a drive allele, or repair by nonhomologous end-joining (NHEJ) produces a drive-resistant allele (R). (B) Drives are predicted to invade by deterministic models when the fitness of DW heterozygotes, $f$, and the homing efficiency, $P$, are in the shaded region. Vertical lines indicate empirical efficiencies from Appendix 1—table 1. (C) Diagram of a single step of the gene-drive Moran process. (D) Finite-population simulations of 15 drive individuals released into a wild population of size 500, assuming conservative ($P=0.5$) or high ($P=0.9$) homing efficiencies, as well as a low-efficiency, constitutively active system ($P=0.15$). Individual sample simulations (solid lines), and 50% confidence intervals (shaded), calculated from ${10}^3$ simulations. Drive-allele frequencies red and resistant-allele frequencies blue. Peak drive, or maximum frequency reached, is illustrated by dashed lines and arrows. (E) Peak drive distributions and medians with varying numbers of individual organisms released (${\displaystyle P=0.5}$). (F) Medians of peak drive distributions for varying homing efficiencies ($P=0.15$, bottom; $P=0.5$, middle; $P=0.9$, top). Throughout, we assume neutral resistance (${\displaystyle f_{WR}=f_{RR}=1}$) and a 10% dominant drive fitness cost ($f_{WD}=f_{DD}=f_{DR}=0.9$).