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Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
YUN Jiaqi, MA Qin, WANG Guandong, SUN Peilu, WANG Yiguan, WANG Sibao
Laboratory Animal and Comparative Medicine ›› 2025, Vol. 45 ›› Issue (6) : 773-783.
PDF(2182 KB)
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Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
Mosquito-borne diseases (such as malaria, dengue fever, Zika virus disease, and Chikungunya) pose major threats to global public health, while traditional control methods based on chemical pesticides face severe challenges including enhanced drug resistance in vector mosquitoes and environmental pollution. Genetic control strategies have become high-potential alternative solutions for mosquito control due to their species specificity and environmental friendliness. Gene drive technology uses gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) to enable specific genes to efficiently spread in target mosquito populations through "super-Mendelian inheritance", offering a revolutionary strategy for the prevention and control of mosquito-borne diseases. This review systematically summarizes key advances, core challenges, and response strategies of gene drive technology in this field. Research advances: (1) In Anopheles malaria vectors, population suppression drives targeting sex determination genes or female reproductive genes can cause female sterility or skewed sex ratios to achieve population suppression. Population replacement gene drive strategies targeting host genes associated with Plasmodium infection or delivering anti-Plasmodium effector molecules in Anopheles can effectively block pathogen transmission. (2) In Aedes mosquito vectors of arboviruses, targeting female flight-essential genes achieves population suppression, and coupling of antiviral effector systems with drive elements is explored. Optimized split gene drive strategies demonstrate high cutting and recombination efficiency, and models predict safe and controllable spread of disease-resistance traits. (3) In Culex mosquitoes transmitting lymphatic filariasis, homology drive elements are integrated into two genes involved in the eye pigment synthesis pathway, allowing clear visualization of gene drive efficiency through eye color. Core Challenges: technological challenges include low homologous recombination repair efficiency, non-homologous end joining repair causing resistance allele generation, CRISPR/Cas9 off-target effects, and species adaptation differences. Ecological and safety challenges involve gene pool pollution caused by accidental spread of drive elements, potential ecological balance impacts, and long-term irreversible risks. Response strategies and prospects: employing multiplex guide RNA (gRNA) targeting strategies to enhance drive stability and combat potential resistance. Developing reversible designs such as synthetic resistance, reversal drives, and immunizing reversal drives as "genetic brakes". Establishing long-term ecological monitoring systems and mathematical modeling for risk assessment. Exploring "environmentally responsive drives" to enhance controllability. Future research should continuously optimize drive efficiency and specificity, deepen ecological risk evaluation, strengthen international cooperation, and promote ethical consensus and regulatory framework construction, with the aim of making gene drive technology a sustainable prevention and control strategy to address the global health challenge of mosquito-borne diseases under the premise of safety and controllability.
Gene drive / Mosquito-borne diseases / Population suppression/population replacement / CRISPR/Cas9
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