Malaria is a devastating disease that causes more than 400,000 deaths each year, primarily in underprivileged regions of sub-Saharan Africa. During the last two decades, mortality caused by the disease has been reduced by half, largely driven by coordinated vector control based on the use of insecticides and bed nets. Nevertheless, the declining trend in malaria cases appears to have stalled recently and there is a growing concern that new interventions will be needed to reach widespread malaria elimination. Gene drive systems are potentially transformative in this endeavour because they allow rapid, self-sustaining and species-specific control of the mosquito vector through the limited release of genetically modified mosquitoes. While proof-of-principle studies have demonstrated the feasibility of the approach, none of them have managed to fulfil the requirements needed to progress in field or semi-field testing, largely due to strong fitness costs and genetic resistance to gene drive. This thesis describes the first gene drive system demonstrated to spread in caged populations of Anopheles gambiae mosquitoes, unimpeded by resistance or fitness constraints. By targeting an ultra-conserved locus in the gene doublesex, this strategy is able to thwart target site resistance in caged experiments whilst driving complete population suppression through the conversion of genetic females to sterile intersex. In this thesis, I demonstrate complete population elimination of caged populations from single releases of gene drive mosquitoes using a 12.5% initial allele release frequency, and crucially, I demonstrate its effectiveness in large cage semi-field conditions designed to reveal complex behaviours otherwise absent in small scale testing. The complete suppression of vector populations using a gene system is a landmark achievement and brings the gene drive technology closer to be implemented in the wild to complement current interventions against malaria.