Mosquito Gene Drives and the Malaria Eradication Agenda

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Section I: The Malaria Challenge
	Chapter 1: Current Scenario of Malaria and the Transformative Power of Gene Drive-Based Technologies
		1.1: Implementation of Malaria Control: Priorities and Constraints
		1.2: Malaria Prevention by Novel Control Methods
		1.3: Population Suppression vs Population Modification
Section II: Mosquito Genetic Manipulation for Malaria
	Chapter 2: Transgenesis and Paratransgenesis for the Control of Malaria
		2.1: Transgenesis
			2.1.1: Tissue-Specific Promoters
			2.1.2: Effector Genes
				2.1.2.1: Peptides/proteins
				2.1.2.2: Antibodies
				2.1.2.3: Mosquito immune genes
		2.2: Paratransgenesis
		2.3: Prospects
	Chapter 3: Gene Drives for Anopheles Mosquitoes
		3.1: Introduction to Gene Drives and Their Characteristics
			3.1.1: The Concept of Gene Drive and Its Applications
			3.1.2: Outcomes of a Gene Drive Strategy
			3.1.3: Confinement of a Gene Drive to Target Populations
		3.2: Types of Gene Drive
			3.2.1: Chromosomal Rearrangements
			3.2.2: Transposons
			3.2.3: Homing Drives
			3.2.4: X-Shredders
			3.2.5: RNAi-Based Toxin-Antidote Drives
			3.2.6: CRISPR-Based Toxin-Antidote Drives
			3.2.7: Wolbachia
	Chapter 4: Gene Drive Applications for Malaria Control
		4.1: Introduction
		4.2: Gene-Drive Applications
			4.2.1: Population Suppression
			4.2.2: Population Modification (Replacement/Alteration)
			4.2.3: Considerations
			4.2.4: Pathways to Deployment
Section III: Gene Drive Mosquito Trials
	Chapter 5: Large Cage Trials of Gene Drive Mosquitoes: Does Size Matter?
		5.1: Introduction
		5.2: Large-Cage Trials Are Widely Advised
		5.3: Case Studies
			5.3.1: Case Study 1: Success after Only Small Cage Studies: Culex pipiens in Burma
			5.3.2: Case Study 2: Success after Preliminary Cage Studies: Culex quinquefasciatus in Florida
			5.3.3: Case Study 3: Failure without Cage Trials: Aedes aegypti in Florida
			5.3.4: Case Study 4: Failure without Large Cage Trials: Anopheles gambiae in Burkina Faso
			5.3.5: Case Study 5: Indoor Cage Trials Were Encouraging but Outdoor Cage Studies in Mexico Ended Development
			5.3.6: Case Study 6: Culex tarsalis in California, USA
			5.3.7: Case Study 7: Anopheles gambiae Ag(DSM)2
			5.3.8: Case Study 8: Anopheles albimanus in El Salvador
		5.4: Colonization Considerations
		5.5: Defining ‘Large’
		5.6: Conclusion
	Chapter 6: Field Trial Site Selection for Mosquitoes with Gene Drive: Geographic, Ecological, and Population Genetic Considerations
		6.1: Introduction
		6.2: Defining the Goal
		6.3: Framework for Field Site Selection
			6.3.1: Physical Features
			6.3.2: Biological Features
		6.4: Evaluation of Potential Island Field Sites
			6.4.1: Evaluation of Tier 1 Criteria
			6.4.2: Other Considerations – Tier 2 Criteria
			6.4.3: Other Considerations – Tier 3 Criteria
		6.5: Conclusion
	Chapter 7: Modeling Priorities as Gene Drive Mosquito Projects Transition from Lab to Field
		7.1: Introduction
		7.2: Model Building
			7.2.1: Population Genetics Models
			7.2.2: Mosquito Vector Models
				7.2.2.1: Mosquito life cycle
				7.2.2.2: Spatial population structure
				7.2.2.3: Density dependence
				7.2.2.4: Movement ecology
				7.2.2.5: Dry season ecology
			7.2.3: Malaria Transmission Models
		7.3: Model Application
			7.3.1: Target Product Profiles
			7.3.2: Monitoring and Surveillance
			7.3.3: Risk and Regulatory Considerations
			7.3.4: Cage Trials
			7.3.5: Field Trial Design
			7.3.6: Intervention Design
		7.4: Conclusion
Section IV: Risk Assessment and Community Engagement
	Chapter 8: Probabilistic Ecological Risk Assessment: An Overview of the Process
		8.1: Introduction
		8.2: Stakeholders, Planning, and Problem Formulation
		8.3: The GMO and Receiving Environment
		8.4: Estimating the Probability and Consequences of Adverse Outcomes
			8.4.1: Models and Risk Assessment
			8.4.2: Probabilistic Risk Assessment Methods
		8.5: Risk Calculations
		8.6: Monitoring, Management, and Acceptability
			8.6.1: Risk Acceptance
			8.6.2: Monitoring and Management
		8.7: Concluding Remarks
	Chapter 9: Community Engagement and Mosquito Gene Drives
		9.1: Introduction
		9.2: Defining Engagement
		9.3: Importance of Engagement
		9.4: General Engagement Considerations
			9.4.1: Funding
			9.4.2: Timeline
			9.4.3: Risks
		9.5: Implementing Engagement
			9.5.1: Identifying Stakeholders
			9.5.2: Identifying a Model/Strategy for Engagement
			9.5.3: Understanding Responsibilities
		9.6: RBM for Engagement
		9.7: RBM, Context, and Concepts
		9.8: Applying the RBM
			9.8.1: Commitment to the Model
			9.8.2: Interdisciplinary Approach
			9.8.3: Build on Existing Strengths and Resources
			9.8.4: Environment for Building/Strengthening Relationships
			9.8.5: Relationship-Based Engagement Planning, Development, and Implementation
			9.8.6: Continuous Evaluation and Improvement
			9.8.7: Capacity Building
		9.9: Conclusion
Section V: Policy, Regulatory, and Ethical Considerations
	Chapter 10: Review of International Regulatory Instruments and Processes
		10.1: Introduction
		10.2: International Regulatory Framework and Current Developments
			10.2.1: CBD
				10.2.1.1: Biotechnology provisions
				10.2.1.2: Developments under the CBD related to gene drives
			10.2.2: Cartagena Protocol
				10.2.2.1: Definitions & scope
				10.2.2.2: National implementation
				10.2.2.3: Risk assessment
		10.3: Regulatory and Policy Developments
			10.3.1: International Developments
				10.3.1.1: Scientific community
				10.3.1.2: LM (and non-LM) mosquitoes
				10.3.1.3: World Health Organization (WHO)
				10.3.1.4: Organization for Economic Co-operation and Development (OECD)
			10.3.2: Regional Developments
				10.3.2.1: African Union (AU)
		10.4: Conclusion
	Chapter 11: Gene Drive Mosquitoes: Ethical and Political Considerations
		11.1: Introduction
		11.2: Slippery Slope of Research
		11.3: Precautionary Principle
		11.4: Conventional Alternatives
		11.5: Environmental Ethics
		11.6: Hubris
		11.7: Public Participation
		11.8: Distributive Justice
		11.9: The Dual Use Dilemma
		11.10: Conclusion
Index