Fig 2 - uploaded by John M Marshall
Content may be subject to copyright.
1 (a) The use of Wolbachia as a means for both population suppression (incompatible insect technique, IIT) and population replacement hinges on the inheritance pattern in which crosses between Wolbachia-infected males and uninfected females produce unviable offspring due to cytoplasmic incompatibility (CI), while crosses involving Wolbachia-infected females produce Wolbachia-infected offspring due to Wolbachia being maternally inherited. (b) In IIT, Wolbachia-infected males are released into a wild population lacking that strain of Wolbachia. This leads to population suppression as mating events involving Wolbachia-infected males produce no viable offspring. (c) In Wolbachia-based population replacement, Wolbachia-infected females are included in the release. This leads to population replacement as CI biases inheritance in favor of Wolbachia when Wolbachia-infected females are present

1 (a) The use of Wolbachia as a means for both population suppression (incompatible insect technique, IIT) and population replacement hinges on the inheritance pattern in which crosses between Wolbachia-infected males and uninfected females produce unviable offspring due to cytoplasmic incompatibility (CI), while crosses involving Wolbachia-infected females produce Wolbachia-infected offspring due to Wolbachia being maternally inherited. (b) In IIT, Wolbachia-infected males are released into a wild population lacking that strain of Wolbachia. This leads to population suppression as mating events involving Wolbachia-infected males produce no viable offspring. (c) In Wolbachia-based population replacement, Wolbachia-infected females are included in the release. This leads to population replacement as CI biases inheritance in favor of Wolbachia when Wolbachia-infected females are present

Source publication
Chapter
Full-text available
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiti...

Citations

... Systems have also been designed to either turn on or turn off gene drive activity in the presence or absence of small organic molecules that can easily enter cells (Heffel and Finnigan, 2019;López Del Amo et al., 2020). While reversal and inducible engineered gene drive systems hold promise for risk management, developers themselves caution against unforeseen consequences (Xu et al., 2020), and indicate that reversal engineered gene drives may not necessarily be the first choice for remediation efforts due to the associated uncertainty of introducing another gene drive approach (Marshall and Vasquez, 2021). ...
... Implementing a modular, phased approach to authorisations for nonlocalised and self-sustaining engineered gene drives remains conceptual at present, in part due to their current inability for recall. Therefore, developers and potential applicants may wish to consider the utility of prior field testing of a closely related self-limiting and/or localised strain as an intermediate step to gather evidence for model development and refinement, and reduce uncertainty in risk assessment (James et al., 2018;EFSA et al., 2020a;Marshall and Vasquez, 2021;WHO, 2021). Self-limiting and/or localisation approaches could be used as biological or molecular risk mitigation strategies to limit the spread and/or persistence of engineered gene drives. ...
Article
Full-text available
The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered gene drives could potentially be used to address long-standing challenges in the control of insect disease vectors, agricultural pests and invasive species, or help to rescue endangered species. However, risk concerns and uncertainty associated with potential environmental release of gene drive modified insects (GDMIs) have led some stakeholders to call for a global moratorium on such releases or the application of other strict precautionary measures to mitigate perceived risk assessment and risk management challenges. Instead, we provide recommendations that may help to improve the relevance of risk assessment and risk management frameworks for environmental releases of GDMIs. These recommendations include: (1) developing additional and more practical risk assessment guidance to ensure appropriate levels of safety; (2) making policy goals and regulatory decision-making criteria operational for use in risk assessment so that what constitutes harm is clearly defined; (3) ensuring a more dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modelling and post-release monitoring; (4) considering potential risks against potential benefits, and comparing them with those of alternative actions to account for a wider (management) context; and (5) implementing a modular, phased approach to authorisations for incremental acceptance and management of risks and uncertainty. Along with providing stakeholder engagement opportunities in the risk analysis process, the recommendations proposed may enable risk managers to make choices that are more proportionate and adaptive to potential risks, uncertainty and benefits of GDMI applications, and socially robust.
... Systems have also been designed to either turn on or turn off GD activity in the presence or absence of small organic molecules that can easily enter cells [50,51]. While reversal and inducible GD systems hold promise, developers themselves caution against unforeseen consequences [49], and indicate that reversal GDs may not necessarily be the first choice for remediation efforts due to the associated uncertainty of introducing another GD approach [52]. ...
... Currently, there is limited direct experience in conducting the risk assessment of GDMI releases. Nonetheless, principles and methodologies for risk assessment and risk management, experience from the risk assessment of GMIs that do not contain engineered GDs, and knowledge from other disease vector and pest control strategies, are relevant to performing GDMI risk assessments [3,15,52]. For example, there is substantial experience with releasing insects for genetic and biological disease vector/pest control, including their risk assessment and post-release monitoring (where applicable), from which lessons can be learnt. ...
... Since self-sustaining engineered GDs are designed for widespread and long-standing control, spatially and/or temporally restricting their spread/persistence would not necessarily be in line with the intended outcome of their release. Therefore, besides gathering data under confined conditions, developers and potential applicants may wish to consider the utility of prior field testing of a related self-limiting strain (note however, that there should be a strong resemblance between the two systems, to the extent possible) as an intermediate step to gather evidence for model development and refinement, and reduce uncertainties in risk assessment [15,16,52]. ...
Article
Full-text available
Potential future application of engineered gene drives (GDs), which bias their own inheritance and can spread genetic modifications in wild target populations, has sparked both enthusiasm and concern. Engineered GDs in insects could potentially be used to address long-standing challenges in control of disease vectors, agricultural pests and invasive species, or help to rescue endangered species, and thus provide important public benefits. However, there are concerns that the deliberate environmental release of GD modified insects may pose different or new harms to animal and human health and the wider environment, and raise novel challenges for risk assessment. Risk assessors, risk managers, developers, potential applicants and other stakeholders at many levels are currently discussing whether there is a need to develop new or additional risk assessment guidance for the environmental release of GD modified organisms, including insects. Developing new or additional guidance that is useful and practical is a challenge, especially at an international level, as risk assessors, risk managers and many other stakeholders have different, often contrasting, opinions and perspectives toward the environmental release of GD modified organisms, and on the adequacy of current risk assessment frameworks for such organisms. Here, we offer recommendations to overcome some of the challenges associated with the potential future development of new or additional risk assessment guidance for GD modified insects and provide considerations on areas where further risk assessment guidance may be required.