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