Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi

TY - JOUR

T1 - Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi

AU - Larrosa Godall, Mireia

AU - Ang Xin De, Joshua

AU - Leftwich, Philip

AU - Gonzalez Fernandez, Estela

AU - Shackleford, Lewis

AU - Nevard, Katherine

AU - Noad, Rob

AU - Anderson, Michelle

AU - Alphey, Luke Stephen

N1 - © The Author(s) 2025

PY - 2025/2/7

Y1 - 2025/2/7

N2 - Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012 it has invaded several countries of eastern Africa, being an emerging risk in causing urban outbreaks, requiring urgent efforts to develop novel and more efficient strategies for targeted vector control. With the emergence of insecticide resistance, CRISPR/Cas9-based homing gene drives have been proposed as viable alternative strategies. In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). The drive, in the presence of Cas9 under the control of the zpg endogenous promoter, was able to home and spread in a super-Mendelian rate comparable to the one obtained by an autonomous drive. Although inheritance rates as high as 99.8% would spread the gene drive into wild populations, observed disruption of male and female heterozygotes’ fertility due to the disruption of the dsxF and dsxM canonical splicing in the presence of the transgene would hinder this spread. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in An. stephensi.

AB - Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012 it has invaded several countries of eastern Africa, being an emerging risk in causing urban outbreaks, requiring urgent efforts to develop novel and more efficient strategies for targeted vector control. With the emergence of insecticide resistance, CRISPR/Cas9-based homing gene drives have been proposed as viable alternative strategies. In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). The drive, in the presence of Cas9 under the control of the zpg endogenous promoter, was able to home and spread in a super-Mendelian rate comparable to the one obtained by an autonomous drive. Although inheritance rates as high as 99.8% would spread the gene drive into wild populations, observed disruption of male and female heterozygotes’ fertility due to the disruption of the dsxF and dsxM canonical splicing in the presence of the transgene would hinder this spread. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in An. stephensi.

U2 - 10.1186/s13071-025-06688-0

DO - 10.1186/s13071-025-06688-0

M3 - Article

SN - 1756-3305

VL - 18

JO - Parasites & vectors

JF - Parasites & vectors

M1 - 46

ER -