Suppression of female fertility in Aedes aegypti with a CRISPR-targeted male-sterile mutation

Aedes aegypti are mosquitoes that transmit dengue and other viruses that infect millions of people annually. One approach to control Ae. aegypti is through the release of sterile males, which suppresses fertilization by fertile males following mating with sterile males. To generate sterile males, the current approach is to mutagenize mosquitoes nonspecifically, which reduces the health of the males. Here, we used genome editing to selectively disrupt a gene (B2t) that specifically affects male fertility. The mutant males were healthy and were effective in suppressing females from producing progeny with fertile males. These studies raise the possibility that the B2t mutation can be employed to improve the sterile insect technique and reduce diseases spread by Ae. aegypti.Aedes aegypti spread devastating viruses such as dengue, which causes disease among 100 to 400 million people annually. A potential approach to control mosquito disease vectors is the sterile insect technique (SIT). The strategy involves repeated release of large numbers of sterile males, which reduces insect populations because the sterile males mate and thereby suppress the fertility of females that would otherwise mate with fertile males. While SIT has been successful in suppressing certain agricultural pests, it has been less effective in depressing populations of Ae. aegypti. This limitation is in part because of the fitness effects resulting from mutagenizing the mosquitoes nonspecifically. Here, we introduced and characterized the impact on female fertility of an Ae. aegypti mutation that disrupts a gene that is specifically expressed in testes. We used CRISPR/Cas9 to generate a null mutation in the Ae. aegypti β2-tubulin (B2t) gene, which eliminates male fertility. When we allowed wild-type females to first mate with B2t mutant males, most of the females did not produce progeny even after being subsequently exposed to wild-type males. We also introduced B2t mutant and wild-type males simultaneously with wild-type females and found that a larger number of B2t mutant males relative to the wild-type males was effective in significantly suppressing female fertility. These results raise the possibility of employing B2t sterile males to improve the efficacy of SIT in suppressing populations of Ae. aegypti through repeated releases and thereby reduce the transmission of viruses by these invasive mosquitoes.All study data are included in the main text.

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