Abstract

Malaria remains a leading public health threat, with more than 249 million cases and over 600,000 deaths reported 
globally in 2022, primarily in sub-Saharan Africa. Traditional vector control tools such as insecticide-treated nets 
and indoor residual spraying have reduced transmission but are increasingly undermined by insecticide resistance 
and ecological shifts. CRISPR-Cas9 gene drive technology has emerged as a transformative approach to target 
mosquito vectors at the population level. The purpose of this review is to examine recent advances in CRISPR-Cas9 
gene drive systems for malaria vector control, highlighting biological mechanisms, experimental progress, and 
implementation challenges. This review synthesized peer-reviewed studies from PubMed, Web of Science, and 
Scopus, focusing on molecular design, laboratory and semi-field studies, and ecological as well as ethical evaluations 
of gene drives. Evidence indicated that homing-based drives targeting fertility genes in Anopheles gambiae can achieve 
greater than 95% inheritance bias and drive population suppression within 10–15 generations in laboratory cages. 
Population modification drives encoding antimalarial effectors demonstrate transmission-blocking efficacy with up 
to 98% reduction in Plasmodium falciparum sporozoite prevalence. However, resistance allele formation, ecological 
unpredictability, and governance gaps remain substantial barriers. While gene drives hold promises as cost-effective, 
sustainable tools complementing current interventions, their translation requires robust regulatory frameworks, 
community engagement, and careful integration with broader malaria elimination strategies. This review concludes 
that CRISPR-Cas9 gene drives represent both scientific opportunity and policy challenge, necessitating 
multidisciplinary collaboration to ensure responsible deployment. 
Keywords: CRISPR-Cas9, Gene drive, Malaria, Anopheles gambiae, Vector control