Researchers explored the use of genetically modified mosquitoes as a potential method of controlling vector-borne diseases.
Last month, Oxitec began releasing its genetically modified (GM), self-limiting male mosquitoes Aedes aegypti in the Florida Keys in hopes of reducing the mosquito population.
This month, WHO released the second edition of its guidelines for testing genetically modified mosquitoes (GMMs), updating the guidelines that were originally published in 2014. We spoke with Jan Kolaczinski, PhD, MSc, head of the vector control and insecticide resistance unit of the WHO Global Malaria Program, on the new directions and what they mean for researchers.
Healio: What are the main issues addressed by the guidelines?
Kolaczinski: There have been major research advancements that increase the feasibility of GMM interventions, with many different possibilities of using this approach being investigated. The characteristics of the different GM strategies need to be taken into account in how they would be tested and how they might be used. The updated guide describes best practices for safety and efficacy testing, ethical and commitment obligations, and regulatory oversight for different types of GMMs at each phase of the testing pathway for different types of GMMs.
Healio: What has changed in the world of GMM research since the guide was first written in 2014, and how has the directions changed to reflect this?
Kolaczinski: The first two papers using CRISPR / Cas for gene drive in mosquitoes were published in late 2015 and early 2016 after publication of the guide. Before that, people tried to exploit natural drive mechanisms with limited success. Advances in gene drive became very rapid with the advent of CRISPR / Cas, and now many types are being considered, including those that are designed to be self-limiting and those that are self-sustaining. Examples of these different types of modifications are provided in the guide. In addition to substantial technical progress, much greater attention has been paid to risk assessment as well as ethical and governance issues for these new types of technologies. We have become much more sophisticated in our thinking about stakeholder engagement in general and perhaps in particular in the context of risk assessment. All of these changes are reflected in the updated guidelines.
Healio: Which technologies are already tested in nature and which other technologies are the most advanced development?
Kolaczinski: The self-limiting mosquitoes produced by Oxitec are the most advanced in terms of field evaluation. The first version of Oxitec’s non-viable GMM for population suppression was tested in small-scale versions by 2014. Now there has been larger-scale testing, and Oxitec has moved on to a product. second generation more effective, fertile and intended to slightly last the suppressant effect in the local mosquito population, but eventually disappear. Fertile male releases Aedes aegypti are currently under evaluation in Florida. No construction of an anopheles mosquito is yet available for field evaluation.
Target Malaria carried out a very small one-site release of a sterile male version of its technology in Burkina Faso as part of its local capacity building activities for future trials.
No GMM containing gene drive has so far been released in the field. The developers have made a lot of progress in creating candidates for gene drive approaches and demonstrating their effectiveness in the laboratory or insectarium, but it is recognized that a lot of additional groundwork needs to be done before these can be done. field tested, as described in the guide.
Wolbachia the work is much more advanced and provided a great deal of real world experience which was informative.
A population suppression strategy using irradiation rather than genetic manipulation to sterilize mosquitoes has been tested in the field.
Healio: What do the councils say More precisely on mosquitoes modified by gene drive?
Kolaczinski: The updated guide includes a much broader review of the progress and challenges facing genetically modified mosquitoes. It examines the implications of different types of gene drive on the staged testing route proposed in 2014. For example, it explains how the propagation characteristics of gene drive should be taken into account in the design of field trials. It discusses how the characteristics of propagation and persistence in the environment should be taken into account in the risk assessment, reviews existing guidance and recommendations from other sources on this issue and recommends how the Risk assessment and management should be addressed at each testing phase. It also reviews relevant precedents for regulatory oversight of gene drive mosquitoes. These include not only the biosafety regulation resulting from the Cartagena Protocol, but also the regulation of biological control agents, which also persist and spread in the environment, and of course, the health regulatory pathways applicable to the tools. public health. As mentioned earlier, the updated guide describes best practices for safety and efficacy testing, ethical and commitment obligations, and regulatory oversight for different types of GMMs, including different types of genetically engineered mosquitoes. at each phase of the test channel.
Healio: Can GMM to end mosquito-borne diseases?
Kolaczinski: We have learned from experience that vector-borne diseases are very resistant, which is why we need as many interventions as possible to combat them in the form of intervention packages tailored to specific contexts. At this point, no one expects GMMs to be a quick fix to ending malaria or arboviral infections. But they have certain theoretical advantages which make them very attractive in addition to existing or planned interventions. For example, they provide region-wide protection that is independent of socio-economic status or proximity to medical facilities; they don’t force people to change their behavior in order to be effective; they can reach hard-to-find mosquito breeding sites and should be effective against outdoor and diurnal vectors that are not targeted by long-lasting insecticidal nets and residual indoor spraying; and they are suitable for both urban and rural disease transmission settings. Those who are self-sufficient should provide long-lasting protection that would reduce delivery costs, allow them to operate in conditions where other interventions are difficult to maintain (such as during civil unrest or the COVID-19 pandemic), and contribute to efforts. disease eradication by providing continued protection against resurgence in areas where the disease has been eliminated. Given these potential benefits and the fact that GMM technologies now appear to be technically feasible, but understanding the need to conduct a thorough assessment of any possible risk on a case-by-case basis, WHO felt that these technologies merited further investigation. .
DiabatÃ© A. Results of several months of surveillance after the first release of non-drive-in genetically modified mosquitoes in Africa. https://targetmalaria.org/results-from-months-of-monitoring-following-the-first-release-of-non-gene-drive-gÃ©nÃ©tique-modified-mosquitoes-in-africa/#:~:text= Objective% 20Malaria% 20Burkina% 20Faso% 20is, version% 20over% 202019% 20and% 202020. Accessed May 24, 2021.
Oxitec. Historic mosquito-borne disease control project kicks off in the Florida Keys. https://www.oxitec.com/en/news/landmark-project-to-control-disease-carrying-mosquitoes-kicks-off-in-the-florida-keys. Accessed May 24, 2021.
WHO. Evaluation of genetically modified mosquitoes for the control of vector-borne diseases. https://www.who.int/publications/i/item/9789240013155. Accessed May 24, 2021.