Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
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Gene drives for vertebrate pest control: realistic spatial modelling of eradication probabilities and times for island mouse populations

20171
A. Birand, P. Cassey, J. V. Ross, J. C. Russell, P. Thomas and T. A. A. Prowse,  Molecular Ecology,  2022-01-24 09:06:03.
Abstract Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used to suppress or eradicate pest populations. We develop an individual-based, spatially explicit, stochastic model to simulate the ability of CRISPR-based homing and X-chromosome shredding drives to eradicate populations of invasive house mice (Mus muculus) from islands. Using the model, we explore the interactive effect of the efficiency of the drive constructs and the spatial ecology of the target population on the outcome of a gene-drive release. We also consider the impact of polyandrous mating and sperm competition, which could compromise the efficacy of some gene-drive strategies. Our results show that both drive strategies could be used to eradicate large populations of mice. Whereas parameters related to drive efficiency and demography strongly influence drive performance, we find that sperm competition following polyandrous mating is unlikely to impact the outcome of an eradication effort substantially. Assumptions regarding the spatial ecology of mice influenced the probability of and time required for eradication, with short-range dispersal capacities and limited mate-search areas producing `chase' dynamics across the island characterised by cycles of local extinction and recolonization by mice. We also show that highly efficient drives are not always optimal, when dispersal and mate-search capabilities are low. Rapid local population suppression around the introduction sites can cause loss of the gene drive before it can spread to the entire island. We conclude that, although the design of efficient gene drives is undoubtedly critical, accurate data on the spatial ecology of target species is critical for predicting the result of a gene-drive release.

A natural fungal gene drive enacts killing through targeting DNA

20215
A. S. Urquhart and D. M. Gardiner,  bioRxiv,  2022.01.19.477016. 2022-01-22 16:24:43.
Fungal spore-killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here we overcome these experimental barriers by developing model systems in two evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast). Using these systems, we show that the Podospora anserina spore killer protein Spok1 enacts killing through targeting DNA.Significance Statement Natural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi these loci are called spore-killers. Despite their importance in evolutionary processes and possible applications our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.Competing Interest StatementThe authors have declared no competing interest.

Recently introduced Wolbachia reduces bacterial species richness and reshapes bacterial community structure in Nilaparvata lugens

20141
T.-P. Li, C.-Y. Zhou, J.-T. Gong, Z. Xi and X.-Y. Hong,  Pest Management Science,  2022-01-21 13:28:22.
BACKGROUND Wolbachia has been developed as an effective tool to suppress insect pests and arbovirus transmission. Recently, the brown planthopper Nilaparvata lugens, a serious agricultural pest, has been successfully transinfected with Wolbachia strain wStri from Laodelphax striatellus. However, before conducting the field experiments, the impacts of wStri on the bacterial microbiota in N. lugens and how it differs from native Wolbachia wLug strain have not been clarified. RESULTS Here, we found that wStri reduced bacterial diversity and shaped bacterial community structure more than wLug in both developmental stage and different adult tissues. Overall, the relative abundance of Wolbachia was negatively correlated with bacterial diversity, but the bacterial diversity gradually decreased only when the relative abundance of Wolbachia was higher than 60%. Further analysis found that wStri reduced species richness of other bacteria but not their evenness. wStri infection also affected many bacterial functions (e.g., amino acid metabolism & signaling and cellular processes) in the developmental stages, with a stronger effect than wLug in nymphs. Moreover, although Wolbachia occupied a high relative abundance in infected individuals, Acinetobacter was consistently a core part of microbiome. CONCLUSION These results showed the significant impacts of recently introduced wStri on bacterial microbiota in N. lugens, with the effects differing from native wLug. This study will aid in understanding the relationship between Wolbachia, its host and the host's microbiota, and provide a reference for future field experiments. This article is protected by copyright. All rights reserved.

Ethical Considerations for Gene Drive: Challenges of Balancing Inclusion, Power and Perspectives

20139
A. Kormos, G. C. Lanzaro, E. Bier, V. Santos, L. Nazare, J. Pinto, A. A. dos Santos and A. James,  Frontiers in Bioengineering and Biotechnology,  2022-01-21 13:24:13.
Progress in gene-drive research has stimulated discussion and debate on ethical issues including community engagement and consent, policy and governance, and decision-making involved in development and deployment. Many organizations, academic institutions, foundations, and individual professionals have contributed to ensuring that these issues are considered prior to the application of gene-drive technology. Central topics include co-development of the technology with local stakeholders and communities and reducing asymmetry between developers and end-users. Important questions include with whom to conduct engagement and how to define community acceptance, develop capacity-building activities, and regulate this technology. Experts, academics, and funders have suggested that global frameworks, standards, and guidelines be developed to direct research in answering these important questions. Additionally, it has been suggested that ethical principles or commitments be established to further guide research practices. The challenging and interesting contradiction that we explore here is that the vast majority of these conversations transpire with little or no input from potential end-users or stakeholders who, we contend, should ultimately determine the fate of the technology in their communities. The question arises, whose concerns regarding marginalization, disempowerment, and inequity should be included in discussions and decisions concerning how inequities are perceived and how they may be addressed? At what stage will true co-development occur and how will opinions, perspectives and knowledge held by low-income country stakeholders be applied in determining answers to the questions regarding the ethics being debated on the academic stage? Our opinion is that the time is now.

IMPACTOS AMBIENTAIS DA TÉCNICA DE GENE DRIVE PARA O CONTROLE DE EPIDEMIAS: ALCANCES E LIMITES DO PRINCÍPIO DA PRECAUÇÃO

23875
N. R. Furtado,  PERI Revista de Filosofia,  13. 2022-01-19 09:24:19.
The paper discusses the application of the precautionary principle in the management of environmental risks arising from the use of gene drives to control epidemics. Gene drives consist of a technique for creating genetically modified organisms, which are released into an ecosystem with the aim of spreading certain genetic elements and prevailing over native organisms. Among the possible uses of this technique are the control of epidemics. Despite its benefits, assessing the impact of gene drives on the environment proves to be a challenge. In the field of biotechnology, the socalled precautionary principle was formulated as a strategy to ground decisions whose consequences are uncertain. However, its application raises discussions about the ability to prevent damage from new technologies. Its critics argue that the precautionary mentality could lead to inaction, obstructing scientific development. Thus, this article highlights the contributions of such principle to guide the use of gene drives, while reflecting on its limits, confronting it with an alternative risk management model: the proactionary principle.

Analysis of a Cas12a-based gene-drive system in budding yeast

20029
I. C. Lewis, Y. Yan and G. C. Finnigan,  Access Microbiol,  3:000301. 2022-01-14 09:19:55.
The discovery and adaptation of CRISPR/Cas systems within molecular biology has provided advances across biological research, agriculture and human health. Genomic manipulation through use of a CRISPR nuclease and programmed guide RNAs has become a common and widely accessible practice. The identification and introduction of new engineered variants and orthologues of Cas9 as well as alternative CRISPR systems such as the type V group have provided additional molecular options for editing. These include distinct PAM requirements, staggered DNA double-strand break formation, and the ability to multiplex guide RNAs from a single expression construct. Use of CRISPR/Cas has allowed for the construction and testing of a powerful genetic architecture known as a gene drive within eukaryotic model systems. Our previous work developed a drive within budding yeast using Streptococcus pyogenes Cas9. Here, we installed the type V Francisella novicida Cas12a (Cpf1) nuclease gene and its corresponding guide RNA to power a highly efficient artificial gene drive in diploid yeast. We examined the consequence of altering guide length or introduction of individual mutational substitutions to the crRNA sequence. Cas12a-dependent gene-drive function required a guide RNA of at least 18 bp and could not tolerate most changes within the 5' end of the crRNA.

Effects of Sterile Males and Fertility of Infected Mosquitoes on Mosquito-Borne Disease Dynamics

20097
X. L. Sun, S. Q. Liu, Y. F. Lv and Y. Z. Pei,  Bulletin of Mathematical Biology,  84:33. 2022-01-13 09:37:31.
By studying an infection-age structured model, we consider the effects of releasing sterile males and the fertility of infected mosquitoes on the mosquito-borne diseases transmission including the extinction of mosquitoes, the elimination and persistence of diseases. Firstly, equivalent integral equations are established to prove the well-posedness of solutions. Then, the main results of disease dynamics are given. By taking chikungunya as a numerical simulation example, an optimal releasing threshold is given according to our presupposed control standard. When the fertility disturbance of infected mosquitoes is small, the high releasing amount plays a main role on the control of the disease; however, when the fertility disturbance is large, the initial distributions and the fertility of infected mosquitoes are the key factors to control the disease. Mathematically, the fertility of infected mosquitoes makes the system have complex dynamics with multiple positive equilibria and bistability.

Gene drive communication: exploring experts’ lived experience of metaphor use

20032
B. Nerlich and A. Stelmach,  New Genetics and Society,  2022-01-13 09:20:04.
Metaphors have been crucial in making genetics and genomics public, fromthe code and the book of life to genetic scissors and gene surgery. A newfield is emerging called“gene drive”–a range of controversial technologiesthat can potentially be used for the eradication or conservation of animalspecies. At the same time, metaphors are emerging to talk about thepromises and dangers of“gene drive”. In this article we use thematicanalysis to examine thirty interviews with gene drive science andcommunication experts, and stakeholders, focusing on how they talk abouttheir lived experience of metaphor use in the context of gene drivecommunication, including their struggle to remember salient metaphors andtheir reflections on which metaphors to use and which to avoid. We discussthe significance of ourfindings for research and practice of responsiblescience communication.

Insect Allies – Assessment of a Viral Approach to Plant Genome Editing

20036
K. Pfeifer, J. L. Frieß and B. Giese,  Integrated Environmental Assessment and Management,  2022-01-12 09:38:06.
The DARPA program Insect Allies has already sparked scientific debate concerning technology assessment-related issues, among which the most prevalent is that of dual use potential. As apart from the issues concerning peaceful applications, the technology also provides the blueprint for a potential bioweapon as further evidenced by a recent publication. However, the combination of a virus-induced genetic modification of crop plants in the field using genetically modified insect vectors poses an increased risk potential in comparison to the hitherto existing use of genetically modified organisms. The technology's high depth of intervention enables a number of sources for hazard and a by trend high exposure, but it is also encumbered with notable deficits in knowledge. These issues call for a thorough technology assessment. This article aims to provide an initial characterization from a technology assessment perspective, focusing on potential sources of risk for this novel invasive environmental biotechnology at an early stage of research and development. This article is protected by copyright. All rights reserved.© 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Characterization of the first Wolbachia from the genus Scaptodrosophila, a male-killer from the rainforest species S. claytoni

20034
K. M. Richardson, M. Schiffer, P. A. Ross, J. A. Thia and A. A. Hoffmann,  Insect Science,  2022-01-12 09:30:05.
Abstract The Scaptodrosophila genus represents a large group of drosophilids with a worldwide distribution and a predominance of species in Australia, but there is little information on the presence and impacts of Wolbachia endosymbionts in this group. Here we describe the first Wolbachia infection from this group, wClay isolated from Scaptodrosophila claytoni (van Klinken), a species from the east coast of Australia. The infection is polymorphic in natural populations, occurring at a frequency of around 6%?10%. wClay causes male killing, producing female-biased lines; most lines showed 100% male killing, though in one line it was < 80%. The lines need to be maintained through the introduction of males unless the infection is removed by tetracycline treatment. wClay is transmitted at a high fidelity (98.6%) through the maternal lineage and has been stable in two laboratory lines across 24 generations, suggesting it is likely to persist in populations. The infection has not been previously described but is closely related to the male-killing Wolbachia recently described from Drosophila pandora based on MLST typing and the wsp gene. Male-killing Wolbachia are likely to be common in drosophilids but remain difficult to detect because the infections can often be at a low frequency. This article is protected by copyright. All rights reserved

Reversing insecticide resistance with allelic-drive in Drosophila melanogaster

20085
B. Kaduskar, R. B. S. Kushwah, A. Auradkar, A. Guichard, M. Li, J. B. Bennett, A. H. F. Julio, J. M. Marshall, C. Montell and E. Bier,  Nature Communications,  13:291. 2022-01-12 09:16:33.
A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel (vgsc) gene (often referred to as knockdown resistance or kdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate common kdr mutations in isogenic laboratory Drosophila strains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two different kdr mutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistant kdr mutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.

The prince, the mayor, and the U.S. fish that ate Japan

20103
C. Elliot,  National Geographic,  2022-01-11 16:44:32.
When Crown Prince Akihito visited Chicago on October 3, 1960, his sole request was to visit Shedd Aquarium. Then Mayor Richard J. Daley, an avid angler, presented the prince with a gift that he scooped with a net from one of the tanks himself: 18 bluegills, the official Illinois state fish. The 26-year-old future emperor was already a passionate ichthyologist, and he planned to stock the exotic fish in the moat surrounding his palace, according to accounts in the Chicago Tribune at the time. At windy Chicago O’Hare International Airport the next day with Princess Michiko, Akihito bid the city farewell, carrying a gift that he couldn’t have imagined would cause a decades-long ecological crisis in his homeland. In the intervening six decades, the bluegills became an invasive, species-destroying nightmare, crowding Japanese freshwater lakes and rivers and destroying native fish biodiversity, says Kenji Saitoh, a researcher at the country’s Fisheries Resources and Education Agency. Fortunately, science has marched on in 60 years. Now, Japanese geneticists are experimenting with the gene editing wizardry of CRISPR to sterilize the invasive bluegills. If the initiative succeeds, wildlife managers could use the same technique to rid the U.S. of damaging aquatic invasives such as the Asian carp.

Introgression of the Aedes aegypti red-eye genetic sexing strains into different genomic backgrounds for sterile insect technique applications

20137
A. A. Augustinos , K. Nikolouli , L. D. De La Fuente , M. Misbah-Ul-Haq, D. O. Carvalho and K. Bourtzis,  Frontiers in Bioengineering and Biotechnology,  2022-01-11 13:16:31.
Aedes aegypti is an invasive mosquito species and major vector of human arboviruses. A wide variety of control methods have been employed to combat mosquito populations. One of them is the sterile insect technique (SIT) that has recently attracted considerable research efforts due to its proven record of success and the absence of harmful environmental footprints. The efficiency and cost-effectiveness of SIT is significantly enhanced by male-only releases. For mosquito SIT, male-only releases are ideally needed since females bite, blood-feed, and transmit the pathogens. Ae. aegypti genetic sexing strains (GSS) have recently become available and are based on eye color mutations that were chosen as selectable markers. These genetic sexing strains were developed through classical genetics and it was shown to be subjected to genetic recombination, a phenomenon that is not suppressed in males as is the case in many Diptera. The genetic stability of these GSS was strengthened by the induction and isolation of radiation-induced inversions. In this study, we used the red eye mutation and the inversion Inv35 line of the Ae. aegypti red-eye GSS s and introgressed them in six different genomic backgrounds to develop GSS with the respective local genomic backgrounds. Our goal was to assess whether the recombination frequencies in the strains with and without the inversion are affected by the different genomic backgrounds. In all cases the recombination events were suppressed in all Inv35 GSS strains, thus indicating that the genomic background does not negatively affect the inversion result. The absence of any effect that could be ascribed to genetic differences, enables the introgression of the key elements of the GSS into the local genomic background prior to release to the target areas. Maintaining the local background increases the chances for successful matings between released males and wild females and addresses potential regulatory concerns regarding biosafety and biosecurity.

iGEM and Gene Drives: A Case Study for Governance

20040
P. Millett, T. Alexanian, M. J. Palmer, S. W. Evans, T. Kuiken and K. Oye,  Health Security,  2022-01-11 09:49:06.
Gene drives have already challenged governance systems. In this case study, we explore the International Genetically Engineered Machine (iGEM) competition's experiences in gene drive-related research and lessons in developing, revising, and implementing a governance system. iGEM's experiences and lessons are distilled into 6 key insights for future gene drive policy development in the United States: (1) gene drives deserve special attention because of their potential for widescale impact and remaining uncertainty about how to evaluate intergenerational and transboundary risks; (2) an adaptive risk management approach is logical for gene drives because of the rapidly changing technical environment; (3) review by individual technical experts is limited and may fail to incorporate other forms of expertise and, therefore, must be complemented with a range of alternative governance methods; (4) current laboratory biosafety and biosecurity review processes may not capture gene drive research or its components in practice even if they are covered theoretically; (5) risk management for research and development must incorporate discussions of values and broader implications of the work; and (6) a regular technology horizon scanning capacity is needed for the early identification of advances that could pose governance system challenges.

Lab-scale characterization and semi-field trials of Wolbachia Strain wAlbB in a Taiwan Wolbachia introgressed Ae. aegypti strain

20383
W. L. Liu, H. Y. Yu, Y. X. Chen, B. Y. Chen, S. N. Leaw, C. H. Lin, M. P. Su, L. S. Tsai, Y. Chen, S. H. Shiao, Z. Y. Xi, A. C. C. Jang and C. H. Chen,  PLOS Neglected Tropical Diseases,  16:24. 2022-01-11 08:53:33.
Author summaryPrior to open field release, new genetic approaches that interfere with mosquito abilities and reduce mosquito population density require progressive evaluation both in the laboratory and contained field trials. Trials in contained outdoor systems are thus an important step and allow for evaluation of the effectiveness and reliability of Wolbachia-infected Aedes aegypti (wAlbB-Tw) in settings that incorporate natural environmental variations. We describe a semi-field system designed to study the ability of wAlbB-Tw mosquitoes to suppress local mosquito populations. We provide a protocol for establishing, maintaining, and monitoring Ae. aegypti population densities inside field cages. These results pave the way for the open release of wAlbB-Tw-infected Ae. aegypti mosquitoes in the field. Dengue fever is one of the most severe viral diseases transmitted by Aedes mosquitoes, with traditional approaches of disease control proving insufficient to prevent significant disease burden. Release of Wolbachia-transinfected mosquitoes offers a promising alternative control methodologies; Wolbachia-transinfected female Aedes aegypti demonstrate reduced dengue virus transmission, whilst Wolbachia-transinfected males cause zygotic lethality when crossed with uninfected females, providing a method for suppressing mosquito populations. Although highly promising, the delicate nature of population control strategies and differences between local species populations means that controlled releases of Wolbachia-transinfected mosquitoes cannot be performed without extensive testing on specific local Ae. aegypti populations. In order to investigate the potential for using Wolbachia to suppress local Ae. aegypti populations in Taiwan, we performed lab-based and semi-field fitness trials. We first transinfected the Wolbachia strain wAlbB into a local Ae. aegypti population (wAlbB-Tw) and found no significant changes in lifespan, fecundity and fertility when compared to controls. In the laboratory, we found that as the proportion of released male mosquitoes carrying Wolbachia was increased, population suppression could reach up to 100%. Equivalent experiments in semi-field experiments found suppression rates of up to 70%. The release of different ratios of wAlbB-Tw males in the semi-field system provided an estimate of the optimal size of male releases. Our results indicate that wAlbB-Tw has significant potential for use in vector control strategies aimed at Ae. aegypti population suppression in Taiwan. Open field release trials are now necessary to confirm that wAlbB-Tw mediated suppression is feasible in natural environments.

The Need for a Tiered Registry for US Gene Drive Governance

20003
K. L. Warmbrod, A. L. Kobokovich, R. West, G. K. Gronvall and M. Montague,  Health Security,  2022-01-10 10:08:26.
A great deal of attention has been focused on the potential risks of gene drives, the kinds of biosafety protections they may require, and how they may be reversed; however, less attention has been paid to the systems that would be useful to have in place in the future, when multiple gene drives may be fielded in multiple species, environments, and countries.4-7 The need for coordinated governance of these technologies will become more pressing as gene drive technologies advance and more drives are created to address other vector-borne diseases like the West Nile virus, agricultural pest management, or invasive species. Gene drives carry different inherent risks compared with other genetically modified organisms (GMOs). Existing governance mechanisms for traditional GMOs are insufficient for oversight of gene drives, which require different systems to assess their usefulness and safety. To address the needs for enhanced oversight, we propose a tiered registry system, similar to the clinical trials databases, which can provide government officials, researchers, biotechnology companies, and the public with useful information about ongoing gene drive research or previously released gene drives. Such a resource would enable scientists to confirm that new gene drives would not interfere with existing drives, provide the public with the information needed to make informed decisions concerning consent for release of gene drives, provide researchers with technical information needed to prevent collisions of independent projects modifying the same organism, and provide regulators with information critical for effective oversight. We propose that the US government should implement such a registry for gene drives in the United States, which does not have a robust gene drive regulatory system in place and is not party to the international treaty most relevant for international gene drive regulation, the Convention on Biological Diversity.8 In this commentary, we describe current efforts to safely regulate gene drive and similar genetic technologies worldwide and how the United States could build a tiered registry database that is specifically designed to regulate such technologies throughout a drive's life cycle.

Effect of aneuploidy of a nonessential chromosome on gene expression in maize

19950
X. Shi, H. Yang, C. Chen, J. Hou, T. Ji, J. Cheng and J. A. Birchler,  Plant Journal,  2022-01-07 09:41:30.
The nonessential supernumerary maize B chromosome (B) has recently been shown to contain active genes and be capable of impacting gene expression of the A chromosomes. However, the effect of the B chromosome on gene expression is still unclear. In addition, it is unknown whether the accumulation of the B chromosome would have a cumulative effect on gene expression. To examine these questions, the global expression of genes, microRNAs (miRNAs), and transposable elements (TEs) of leaf tissue of W22 maize (Zea mays) plants with 0 to 7 copies of the B chromosome was studied. All experimental genotypes with B chromosomes displayed a trend of upregulated gene expression for a subset of A-located genes compared to the control. Over three thousand A-located genes are significantly differentially expressed in all experimental genotypes with the B chromosome relative to the control. Modulations of these genes are largely determined by the presence rather than the copy number of the B chromosome. By contrast, the expression of most B-located genes is positively correlated with B copy number, showing a proportional gene dosage effect. The B chromosome also causes increased expression of A-located miRNAs. Differentially expressed miRNAs potentially regulate their targets in a cascade of effects. Furthermore, the varied copy number of the B chromosome leads to the differential expression of A-located and B-located TEs. The findings provide novel insights into the function and properties of the B chromosome.

An Introduction to Containment Recommendations for Gene Drive Mosquitoes and the Laboratory Rearing of Genetically Engineered Mosquitoes in Africa

20044
S. Higgs,  Vector-Borne and Zoonotic Diseases,  2022-01-06 10:04:57.
The prospect of using genetically engineered arthropods to reduce the incidence of vector-borne diseases either indirectly by suppressing vector populations or directly by replacing wild-type vector species with less competent ones has long been discussed; however, only in the past few years has this become feasible. The advent of CRISPR/Cas9-based gene drive and its application to mosquitoes have been a critical factor in bringing the dream to reality, but with opportunity also comes responsibility. Safe and secure handling of genetically engineered arthropods under laboratory/insectary conditions was considered in the original and revised ACGs, and under field conditions by Benedict et al. (2008). Although not discussed in these ACGs, hence the need for this addendum, Benedict et al. (2018) discussed containment and management of gene drive arthropods as distinct from genetically modified mosquitoes under laboratory conditions. A prerequisite for the application of engineered mosquitoes for mosquito-borne disease control is the rearing of these mosquitoes in countries where releases will ultimately occur. In 2018, three companion articles were published in VBZ that discussed this very issue (Mumford et al. 2018, Quinlan et al. 2018a, 2018b), with James et al. (2020) discussing efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing. In this issue of VBZ, we publish two highly relevant articles that coincidentally, although submitted independently, are complementary.

Preparing an Insectary in Burkina Faso to Support Research in Genetic Technologies for Malaria Control

20042
C. Guissou, M. M. Quinlan, R. Sanou, R. K. Ouédraogo, M. Namountougou and A. Diabaté,  Vector-Borne and Zoonotic Diseases,  2022-01-06 09:53:59.
The Institut de Recherche en Sciences de la Santé (IRSS) of Burkina Faso, West Africa, was the first African institution to import transgenic mosquitoes for research purposes. A shift from the culture of mosquito research to regulated biotechnology research and considerable management capacity is needed to set up and run the first insectary for transgenic insects in a country that applied and adapted the existing biosafety framework, first developed for genetically modified (GM) crops, to this new area of research. The additional demands arise from the separate regulatory framework for biotechnology, referencing the Cartagena Protocol on Biosafety, and the novelty of the research strain, making public understanding and acceptance early in the research pathway important. The IRSS team carried out extensive preparations following recommendations for containment of GM arthropods and invested efforts in local community engagement and training with scientific colleagues throughout the region. Record keeping beyond routine practice was established to maintain evidence related to regulatory requirements and risk assumptions. The National Biosafety Agency of Burkina Faso, Agence Nationale de Biosécurité (ANB), granted the permits for import of the self-limiting transgenic mosquito strain, which took place in November 2016, and for conducting studies in the IRSS facility in Bobo-Dioulasso. Compliance with permit terms and conditions of the permits and study protocols continued until the conclusion of studies, when the transgenic colonies were terminated. All this required close coordination between management and the insectary teams, as well as others. This article outlines the experiences of the IRSS to support others undertaking such studies. The IRSS is contributing to the ongoing development of genetic technologies for malaria control, as a partner of Target Malaria (https://targetmalaria.org). The ultimate objective of the innovation is to reduce malaria transmission by using GM mosquitoes of the same species released to reduce the disease-vectoring native populations of Anopheles gambiae s.l.

Beyond the eye: Kynurenine pathway impairment causes midgut homeostasis dysfunction and survival and reproductive costs in blood-feeding mosquitoes

19915
V. Bottino-Rojas, I. Ferreira, R. D. Nunes, X. Feng, T. B. Pham, A. Kelsey, R. Carballar-Lejarazú, V. Gantz, P. L. Oliveira and A. A. James,  Insect Biochemistry and Molecular Biology,  103720. 2022-01-06 08:57:05.
Insect ommochrome biosynthesis pathways metabolize tryptophan to generate eye-color pigments and naturally occurring alleles of pathway genes are useful phenotypic markers in transgenesis studies. Pleiotropic effects of mutations in some genes exert a load on both survival and reproductive success in blood-feeding species. Here, we investigated the challenges imposed on mosquitoes by the increase of tryptophan resulting from blood meal digestion and the impact of disruptions of the ommochrome biosynthesis pathway. Female mosquitoes with spontaneous and induced mutations in the orthologs of the genes encoding kynurenine hydroxylase in Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus exhibited impaired survival and reproductive phenotypes that varied in type and severity among the species. A compromised midgut permeability barrier function was also observed in An. stephensi. Surprisingly, mutant mosquitoes displayed an increase in microbiota compared to controls that was not accompanied by a general induction of immune genes. Antibiotic treatment rescued some deleterious traits implicating a role for the kynurenine pathway (KP) in midgut homeostasis. Supplemental xanthurenic acid, a KP end-product, rescued lethality and limited microbiota proliferation in Ae. aegypti. These data implicate the KP in the regulation of the host/microbiota interface. These pleiotropic effects on mosquito physiology are important in the development of genetic strategies targeting vector mosquitoes.

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