MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics
Fig 4
Example MGDrivE 2 simulations for a split gene drive system designed to drive a malaria-refractory gene in a confinable and reversible manner into an An. gambiae s.l. mosquito population with seasonal population dynamics and transmission intensity calibrated to a setting resembling the island of Grand Comore, Union of the Comoros.
The split drive system resembles one recently engineered in Ae. aegypti [2]–the only split drive system in a mosquito vector to date. In the modeled system, two components–the Cas9 and guide RNA (gRNA)–are present at separate, unlinked loci, and a disease-refractory gene is linked to the gRNA. Four alleles are considered at the gRNA locus: an intact gRNA/refractory allele (denoted by “H”), a wild-type allele (denoted by “W”), a functional, cost-free resistant allele (denoted by “R”), and a non-functional or otherwise costly resistant allele (denoted by “B”). At the Cas9 locus, two alleles are considered: an intact Cas9 allele (denoted by “C”), and a wild-type allele (denoted by “W”). Model parameters describing the construct, mosquito bionomics and malaria transmission are summarized in S1 Table. (A) Climatological time-series data—temperature in red and rainfall in blue—that were used to calculate time-varying adult mosquito mortality rate and larval carrying capacity, respectively. The resulting adult female population size is shown in green. (B) Allele frequencies for adult female mosquitoes over the simulation period. Grey vertical bars beginning at year three denote eight consecutive weekly releases of 50,000 male mosquitoes homozygous for both the gRNA and Cas9 alleles (H and C, respectively). (C) Spread of the malaria-refractory trait through the female mosquito population, and consequences for mosquito and human infection status. Following releases of the drive system at year three, the proportion of refractory female mosquitoes (solid red line) increases and the proportion of infectious mosquitoes (dotted light blue line) declines. As humans recover from infection and less develop new infections, the P. falciparum parasite rate (solid green line) declines until it reaches near undetectable levels by year five. (D) Human malaria incidence is halted by the beginning of year four.