Recent Publications

Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products

Published in Frontiers in Bioengineering and Biotechnology, 2023

Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria and other mosquito-borne diseases, and promising results have been observed from testing conducted in containment. Although still at an early stage of development, it is important to begin now to consider approval procedures and market entry strategies for the eventual implementation of GDMMs in the context of disease control programs, as these could impact future research plans. It is expected that, as for other types of new products, those seeking to bring GDMMs to market will be required to provide sufficient information to allow the regulator(s) to determine whether the product is safe and effective for its proposed use. There already has been much emphasis on developing requirements for the biosafety components of the “safe and effective” benchmark, largely concerned with their regulation as genetically modified organisms. Other potential approval requirements have received little attention, however. Although GDMMs are expected to be implemented primarily in the context of public health programs, any regulatory analogies to other public health products, such as pharmaceuticals, vaccines, or chemical pesticides, must take into account the characteristics of live mosquito products. Typical manufacturing standards related to product identity, potency or quality will need to be adapted to GDMMs. Valuable lessons can be drawn from the regulatory approval processes for other whole organism and genetically modified (GM) organism products. Supply chain requirements, such as scale of production, location and design of production facilities, and methods of distribution and delivery, will be dependent upon the characteristics of the particular GDMM product, the conditions of use, and the region to be served. Plans for fulfilling supply chain needs can build upon experience in the development of other live insect products for use in public health and agriculture. Implementation of GDMMs would benefit from additional research on enabling technologies for long-term storage of mosquito life stages, efficient mass production, and area-wide delivery of GDMMs. Early consideration of these practical requirements for market entry will help to mitigate downstream delays in the development of these promising new technologies. Read more

Recommended citation: James S, Quemada H, Benedict M, Dass B. 2023. Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products. Frontiers in Bioengineering and Biotechnology. Vol 11 (https://doi.org/10.3389/fbioe.2023.1205865)

Regulatory and policy considerations for the implementation of gene drive‑modifed mosquitoes to prevent malaria transmission

Published in Transgenic Research, 2023

Gene drive-modified mosquitoes (GDMMs) are being developed as possible new tools to prevent transmission of malaria and other mosquito-borne diseases. To date no GDMMs have yet undergone field testing. This early stage is an opportune time for developers, supporters, and possible users to begin to consider the potential regulatory requirements for eventual implementation of these technologies in national or regional public health programs, especially as some of the practical implications of these requirements may take considerable planning, time and coordination to address. Several currently unresolved regulatory questions pertinent to the implementation of GDMMs are examined, including: how the product will be defined; what the registration/approval process will be for placing new GDMM products on the market; how the potential for transboundary movement of GDMMs can be addressed; and what role might be played by existing multinational bodies and agreements in authori- zation decisions. Regulation and policies applied for registration of other genetically modified organisms or other living mosquito products are assessed for relevance to the use case of GDMMs to prevent malaria in Africa. Multiple national authorities are likely to be involved in decision-making, according to existing laws in place within each country for certain product classes. Requirements under the Cartagena Protocol on Biodiversity will be considered relevant in most countries, as may existing regulatory frameworks for conventional pesticide, medical, and biocontrol products. Experience suggests that standard regulatory processes, evidence requirements, and liability laws differ from country to country. Regional mechanisms will be useful to address some of the important challenges. Read more

Recommended citation: James, S., Dass, B., Quemada, H. Regulatory and policy considerations for the implementation of gene drive‑modifed mosquitoes to prevent malaria transmission (2023). https://doi.org/10.1007/s11248-023-00335-z

Exploring the value of a global gene drive project registry

Published in Nature Biotechnology, 2022

Recent calls to establish a global project registry before releasing any gene-drive-modified organisms (GDOs) have suggested a registry could be valuable to coordinate research, collect data to monitor and evaluate potential ecological impacts, and facilitate transparent communication with community stakeholders and the general public. Here, we report the results of a multidisciplinary expert workshop on GDO registries convened on 8–9 December 2020 involving 70 participants from 14 countries. Participants had expertise in gene drive design, conservation and population modeling, social science, stakeholder engagement, governance and regulation, international policy, and vector control; they represented 45 organizations, spanning national and local governmental agencies, international organizations, nonprofit organizations, universities, and district offices overseeing local vector control. The workshop aimed to gather perspectives on a central question: “In what ways could a gene-drive project registry both contribute to and detract from the fair development, testing and use of GDOs?” We specifically queried the perceived purpose of a registry, the information that would need to be included, and the perceived value of a registry. Three primary findings emerged from the discussion: first, many participants agreed a registry could serve a coordinating function for multidisciplinary and multisector work activities; second, doing so may require different design elements, depending on the target end-user group and intended purpose for that group; and third, these different information requirements lead to concerns about information sharing via a registry, suggesting potential obstacles to achieving transparency through such a mechanism. We conclude that any development of a gene-drive project registry requires careful and inclusive deliberation, including with potential end-users, to ensure that registry design is optimal. Read more

Recommended citation: Taitingfong R, Triplett C, Vásquez V, Rajagopalan R, Raban R, Roberts A, Terradas G, Baumgartner B, Emerson C, Gould F, Okumu F, Schairer C, Bossin H, Buchman L, Campbe K, Clark A, Delborne J, Esvelt K, Fisher J, Friedman R, Gronvall G, Gurfield N,Heitman L, Kofler N, Kuiken T, Kuzma J, Manrique-Saide P, Marshall J,Montague M, Morrison A, Opesen C, Phelan R,Piaggio A, Quemada H, Rudenko L, Sawadogo N, Smith R, Tuten H, Ullah A, Vorsino A, Windbichler N, Akbari O, Long K, Lavery J, Weiss Evans s, Tountas K & Bloss C. 2022. Exploring the value of a global gene drive project registry. Nature Biotechnology https://doi.org/10.1038/s41587-022-01591-w

Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development

Published in Transgenic Research, 2022

Novel genetically modified biological control products (referred to as “GM biocontrol products”) are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products. Read more

Recommended citation: Tonui, W., Ahuja, V., Beech, C., Connolly, J.,Dass, B., Glandorf, D., James, J., Muchiri, J., Mugoya, C., Okoree, E., Quemada, H., Romeis, J. 2022. Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development. Transgenic Research https://doi.org/10.1007/s11248-022-00311-z

Special Issue: Risk assessment and regulation of gene drive mosquitoes

Published in Transgenic Research, 2022

Transgenic organisms containing constructs that have genetic elements biasing inheritance in their favor are a new tool in moving a specific allele into non-transgenic populations, either managed or–more importantly–in the wild. This new type of transgenic organism (gene drive organism) can potentially benefit agriculture, conservation, and public health. The use of gene drive-containing mosquitoes has received special attention because they are the furthest along experimentally, and because they have the potential to provide a new and sorely-needed tool in the toolbox for eliminating malaria in Africa. However, as with previous transgenic organisms, safety and regulatory questions have been raised. These questions are not necessarily new, but will require answers if gene drive-containing mosquitoes are to gain regulatory approval and public acceptance. There is currently little experience with the risk assessment of the environmental release of gene drive organisms. The lack of a real-world example nearing the field trial stage leaves consideration of risks primarily hypothetical. However, several areas of generic concern connected with the release of mosquitoes containing gene drives, have been identified by formal problem formulation exercises, and can be addressed at this early stage. Furthermore, initial efforts to identify data requirements to address these concerns as they have arisen in the context of generic risk assessments have also been made. Those countries where these mosquito gene drive interventions will be first deployed should develop the necessary regulatory frameworks to properly regulate these organisms, balancing risk and benefit. The existing regulatory structures appropriate for regulating gene drive organisms, should be identified, and the experience gained from regulating other more “traditional” genetically engineered organisms, such as the lessons learned from working with genetically engineered crops, should be leveraged to maximize the regulatory oversight and possible successful deployment of these interventions. This special issue features articles that address these issues. The first one in the series recounts the experience of transgenic crop deployment from the initial cases until today, exploring reasons why public acceptance and government approvals, especially in Africa, has been low, despite the record of safety, and economic and environmental benefits. The lessons learned from this experience and how they might be applied to gene drive deployment are presented. Other articles in this issue will explore particular areas of concern and their likelihood of presenting significant risks: horizontal gene transfer from gene drive-containing mosquitoes, the role of mosquitoes as pollinators, and the potential impact of gene drive mosquitoes on water quality. An article on the points for researchers to consider when they are seeking approvals for laboratory research, field testing, and eventual large-scale environmental release of genetic biocontrol products. It is hoped that this collection of articles can be useful to researchers, policy-makers, and regulators as they develop their products, formulate policies regarding the use, and formulate regulations that assure the safe deployment, respectively, of mosquitoes containing gene drives. Read more

Recommended citation: Quemada, H., Tonui, W.K., de Andrade, P.P., Lema, M.A. eds. Risk assessment and regulation of gene drive mosquitoes. Transgenic Research (2022). https://link.springer.com/collections/dagcafceif

Lessons learned from the introduction of genetically engineered crops: relevance to gene drive deployment in Africa

Published in Transgenic Research, 2022

The application of gene drives to achieve public health goals, such as the suppression of Anopheles gambiae populations, or altering their ability to sustain Plasmodium spp. infections, has received much attention from researchers. If successful, this genetic tool can contribute greatly to the wellbeing of people in regions severely affected by malaria. However, engineered gene drives are a product of genetic engineering, and the experience to date, gained through the deployment of genetically engineered (GE) crops, is that GE technology has had difficulty receiving public acceptance in Africa, a key region for the deployment of gene drives. The history of GE crop deployment in this region provides good lessons for the deployment of gene drives as well. GE crops have been in commercial production for 24 years, since the planting of the first GE soybean crop in 1996. During this time, regulatory approvals and farmer adoption of these crops has grown rapidly in the Americas, and to a lesser extent in Asia. Their safety has been recognized by numerous scientific organizations. Economic and health benefits have been well documented in the countries that have grown them. However, only one transgenic rop event is being grown in Europe, and only in two countries in that region. Europe has been extremely opposed to GE crops, due in large part to the public view of agriculture that opposes “industrial” farming. This attitude is reflected in a highly precautionary regulatory and policy environment, which has highly influenced how African countries have dealt with GE technology and are likely to be applied to future genetic technologies, including gene drives. Furthermore, a mistrust of government regulatory agencies, the publication of scientific reports claiming adverse effects of GE crops, the involvement of corporations as the first GE crop developers, the lack of identifiable consumer benefit, and low public understanding of the technology further contributed to the lack of acceptance. Coupled with more emotionally impactful messaging to the public by opposition groups and the general tendency of negative messages to be more credible than positive ones, GE crops failed to gain a place in European agriculture, thus influencing African acceptance and government policy. From this experience, the following lessons have been learned that would apply to the deployment of gene drives, in Africa: Read more

Recommended citation: Quemada, H. Lessons learned from the introduction of genetically engineered crops: relevance to gene drive deployment in Africa. Transgenic Research (2022). https://doi.org/10.1007/s11248-022-00300-2

Risk management recommendations for environmental releases of gene drive modified insects

Published in Biotechnology Advances, 2021

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. Read more

Recommended citation: Y. Devos, J.D. Mumford, M.B. Bonsall, et al., Risk management recommendations for environmental releases of gene drive modified insects, Biotechnology Advances (2018), https://doi.org/10.1016/j.biotechadv.2021.107807

Guidance Framework for Testing Genetically Modified Mosquitoes, Second Edition

Published in World Health Organization, 2021

This revised version of the Guidance framework for testing of genetically modified mosquitoes, published in 2014, takes into account the technical progress made and lessons learned since then in this rapidly advancing field of research. Like the original Guidance framework, it is intended to provide standards that foster quality and consistency in the processes for developing, testing and regulating these new genetic technologies. Best practices recommended in the 2021 Guidance framework will further contribute to the comparability of results and credibility of conclusions in order to facilitate decision-making by countries interested in the potential use of GMMs as public health tools for the control of vector- borne diseases. Read more

Recommended citation: World Health Organization (2021) Guidance Framework for Testing Genetically Modified Mosquitoes, Second Edition. World Health Organization, Geneva

Regulatory approaches for genome edited agricultural plants in select countries and jurisdictions around the world

Published in Transgenic Research, 2021

Genome editing in agriculture and food is leading to new, improved crops and other products. Depending on the regulatory approach taken in each country or region, commercialization of these crops and products may or may not require approval from the respective regulatory authorities. This paper describes the regulatory landscape governing genome edited agriculture and food products in a selection of countries and regions. Read more

Recommended citation: Entine J., Felipe M.S.S., Groenewald J.H., et al. Regulatory approaches for genome edited agricultural plants in select countries and jurisdictions around the world. Transgenic Research (2021). https://doi.org/10.1007/s11248-021-00257-8.

Regulatory Capacity Strengthening for Gene-Drive Technology Applications for Vector-Borne Disease Control in Africa

Published in Michigan State University WorldTAP Reports, 2020

The use of gene-drive constructs in genetically modified insects has great potential to address malaria vector control in Africa and worldwide. However, they can only be developed and deployed if regulatory agencies have the capacity to properly review and make decisions on this new category of applications of genetic modification technology. This policy brief summarizes the results obtained from the needs assessment for regulatory capacity building for gene-drives in Africa. Read more

Recommended citation: Mbabazi R, Quemada H, Shore S, et al (2020) Regulatory Capacity Strengthening for Gene-Drive Technology Applications for Vector-Borne Disease Control in Africa. Michigan State University

Edit at Will: Genotype Independent Plant Transformation in the Era of Advanced Genomics and Genome Editing

Published in Plant Science, 2019

The combination of advanced genomics, genome editing and plant transformation biology presents a powerful platform for basic plant research and crop improvement. Together these advances provide the tools to identify genes as targets for direct editing as single base pair changes, deletions, insertions and site specific homologous recombination. Recent breakthrough technologies using morphogenic regulators in plant transformation creates the ability to introduce reagents specific toward their identified targets and recover stably transformed and/or edited plants which are genotype independent. These technologies enable the possibility to alter a trait in any variety, without genetic disruption which would require subsequent extensive breeding, but rather to deliver the same variety with one trait changed. Regulatory issues regarding this technology will predicate how broadly these technologies will be implemented. In addition, education will play a crucial role for positive public acceptance. Taken together these technologies comprise a platform for advanced breeding which is an imperative for future world food security. Read more

Recommended citation: Kausch, A.P, Nelson-Vasilchik, K., Hague, J., Mookkan, M., Quemada, H., Dellaporta, S., Fragoso, C., Zhang, A. (2019). Edit at Will: Genotype Independent Plant Transformation in the Era of Advanced Genomics and Genome Editing. Plant Science 218: 186-205

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group

Published in The American Journal of Tropical Medicine and Hygiene, 2018

Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multi- disciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes. Read more

Recommended citation: James, S., Collins, F., Welkhoff, P., Emerson, C., Godfray, H., Gottlieb, M., Greenwood, B., Lindsay, S., Mbogo, C., Okumu, F., Quemada, H., Savadogo, M., Singh, J., Tountas, K., Touré, Y. 2018. Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group. The American Journal of Tropical Medicine and Hygiene 98: 1-49.

Rationalizing governance of genetically modified products in developing countries

Published in Nature Biotechnology, 2018

Ever-more powerful genetic technologies, such as genome-editing endonucleases and marker-assisted breeding, continue to facilitate the development of genetically modified (GM) crops engineered with complex traits, such as, nutritional quality, climatic resilience and stacked disease-tolerance mechanisms. But in many developing countries, the uptake of these GM products is being jeopardized by the sluggish pace and inadequacy of regulatory oversight. Read more

Recommended citation: Adenle, A., Morris, E., Murphy, D., Phillips, P., Trigo, E., Kearns, P., Li, Y-H., Quemada, H., Falck-Zepeda, J., Komen, J. 2018. Rationalizing governance of genetically modified products in developing countries. Nature Biotechnology 36: 137-139.

Hector Quemada

Recent Publications