Mosquito Gene Drives and the Malaria Eradication Agenda

Malaria is one of most serious infectious diseases today and has afflicted humankind for thousands of years. A significant number of people still die from this mosquito-borne disease, despite the use of various malaria prevention and control methods over hundreds of years and more than a century of coordinated global control efforts using modern tools, together with research into and development of new strategies for prevention, diagnosis, and disease treatment. Genetic approaches that focus on the vector mosquitoes to prevent malaria parasite transmission have been considered for many decades. Genetic control strategies received a significant boost with the successful development of gene drive systems, genetic methods for rapidly spreading beneficial genes and phenotypes through mosquito populations. This book reviews some concepts of gene drive systems and describes pioneering applications to control mosquito populations and prevent parasite transmission.

SECTION I THE MALARIA CHALLENGE 1. Current Scenario of Malaria and the Transformative Power of Gene Drive-Based Technologies George Dimopoulos SECTION II MOSQUITO GENETIC MANIPULATION FOR MALARIA 2. Transgenesis and Paratransgenesis for the Control of Malaria Sibao Wang and Marcelo Jacobs-Lorena 3. Gene Drives for Anopheles Mosquitoes Jackson Champer 4. Gene Drive Applications for Malaria Control Vanessa Macias and Anthony James SECTION III GENE DRIVE MOSQUITO TRIALS 5. Large Cage Trials of Gene Drive Mosquitoes: Does Size Matter? Mark Q. Benedict 6. Field Trial Site Selection for Mosquitoes with Gene Drive: Geographic, Ecological, and Population Genetic Considerations Gregory C. Lanzaro et al. 7. Modeling Priorities as Gene Drive Mosquito Projects Transition from Lab to Field John M. Marshall and Ace R. North SECTION IV RISK ASSESSMENT AND COMMUNITY ENGAGEMENT 8. Probabilistic Ecological Risk Assessment: An Overview of the Process Keith R. Hayes, Geoffrey R. Hosack, and Adrien Ickowicz 9. Community Engagement and Mosquito Gene Drives Ana Kormos SECTION V POLICY, REGULATORY, AND ETHICAL CONSIDERATIONS 10. Review of International Regulatory Instruments and Processes Felicity Keiper and Ana Atanassova 11. Gene Drive Mosquitoes: Ethical and Political Considerations Daniel Edward Callies and Athmeya Jayaram

Dr. Rebeca Carballar-Lejarazú’s research is focused on insect molecular genetics, vector biology, and the development of synthetic approaches to prevent transmission of mosquito-borne diseases. She has used several genetic strategies such as transposon-based random integration, phiC31 docking-site integration and CRISPR/Cas9 site-specific genome editing technologies to develop transgenic mosquitoes. Dr. Carballar-Lejarazú is currently working on the development, optimization, and evaluation of a CRISPR/Cas9 gene drive system to engineer mosquitoes that resist malaria parasites (population modification/replacement) in two main malaria African vectors Anopheles gambiae and Anopheles coluzzii. Her insect interests have been centered mainly on vector mosquitoes. However, in 2014, she started a collaboration with Professor Sonqing Wu to study biopesticides to control crop pests in China.