This strategy relies on altering the sex ratio in malaria mosquito populations to decrease the number of female malaria mosquitoes relative to males. Only female Anopheles gambiae transmit the disease, and a reduction in the number of females limits reproduction and the future population size, therefore reducing the number of vectors for malaria
The approach is based around the sex-determining chromosomes (XY for males, and XX for females) and relies on the fact that female offspring require two functional X chromosomes– one from each parent – in order for female offspring to be produced.
Target Malaria researchers have used nuclease enzymes (image 1) to identify and cut through several key sites on the X chromosome (image 2) in the sperm of male Anopheles gambiae which leads to a fragmentation of this chromosome (image 3). When these males reproduce, they can still pass on a functional Y chromosome to their offspring, but they cannot pass on a functional X chromosome due to its fragmentation (image 4). This results in a bias toward male (XY) offspring.
Work published by our team in June 2014 has shown that we can successfully distort the sex ratio of a laboratory population, as over 95% of the offspring produced by modified Anopheles gambiae were male, with only 5% being female. By comparison, under normal circumstances, researchers would expect a 50:50 split between male and females, meaning that our modification reduces the number of females produced by 10-fold.
Mathematical models indicate that the approach could be highly effective in reducing mosquito numbers. Because the modification is intended to be carried on the Y chromosome, it would also be self-sustaining. The male offspring of modified males would remain fertile and every single one of them would have the sex-distorting nuclease gene on their Y chromosome, allowing them to continue the trend of producing mostly male offspring.
Biasing the Sex Ratio