Featured Articles
Pest control gets the CRISPR treatment
33376Seydel, C., Nature Biotechnology, 2024-11-04 13:45:02.
In June 2024, the St. Louis–based pest control company Agragene released genetically modified fruit flies on berry farms in California and Oregon, moving the technology out of the laboratory and into contained field testing. The trial marked a milestone for a next-generation biocontrol technology called the precision-guided sterile insect technique, or pgSIT. “The spotted wing drosophila (SWD) is the number 1 problem for any kind of strawberry, blueberry, raspberry, blackberry grower,” said Bryan Witherbee, president and CEO of Agragene. The flies have developed resistance to conventional chemical pesticides, and fruit growers suffer enormous economic losses due to the pest. “Growers are crying out for new tools,” Witherbee said. Hope is on the horizon, not only for farmers battling SWD and other agricultural pests but also for public health agencies struggling to control disease vectors. Several companies, including Agragene, are bringing biological pest control into the CRISPR era with pgSIT and other molecular tools that can specifically target the pest without killing beneficial insects, polluting the water or blanketing communities with toxic airborne chemicals. San Diego–based Synvect is applying pgSIT to disease-causing mosquitoes. Meanwhile, Oxitec, which has already successfully commercialized its “Friendly” genetic modification platform in mosquitoes, is turning its attention to crop pests.
The potential of gene drives in malaria vector species to control malaria in African environments
32702Hancock, P.A., North, A., Leach, A.W. et al., Nature Communications, 15. 2024-10-22 14:44:25.
Gene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of gene drives that causes vector population suppression. We simulate gene drive releases in sixteen ~ 12,000 km2 areas of west Africa that span variation in vector ecology and malaria prevalence, and estimate reductions in vector abundance, malaria prevalence and clinical cases. Average reductions in vector abundance ranged from 71.6–98.4% across areas, while impacts on malaria depended strongly on which vector species were targeted. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results show that different strategies for gene drive implementation may be required across different African settings.
Professor Abdoulaye Diabaté’s frank conversation with Bill Gates
32512African Media Agency, 2024-10-08 09:27:11.
On October 2, 2024, Professor Abdoulaye Diabaté, a prominent figure in malaria research and Head of Medical Entomology at Burkina Faso’s Research Institute in Health Sciences, gained international attention by appearing in the Netflix documentary series "What’s Next? The Future With Bill Gates." The episode, titled "Can We Outsmart Disease?", delves into the ongoing battle against malaria, which disproportionately affects Africa, accounting for 94% of cases and 95% of deaths globally. In his conversation with Gates, Diabaté highlights the critical link between malaria and poverty, arguing that had the disease claimed similar lives in wealthier nations, it would have prompted a more aggressive global response. He advocates for a greater role for African voices in developing innovative solutions to combat malaria, including emerging technologies like gene drive mechanisms aimed at reducing mosquito populations. Despite significant progress, recent reports indicate a worrying increase in malaria cases due to factors such as insecticide resistance and climate change. The documentary underscores the urgent need for sustained investment in malaria research and innovative approaches, a sentiment echoed by Gates, who notes the shocking disparity in funding for malaria compared to other health issues. As the series aims to raise awareness and inspire action, it poses a pressing question: Can we finally outsmart this persistent disease?
Advancements and Future Prospects of CRISPR-Cas-Based Population Replacement Strategies in Insect Pest Management
31330Zhao Y, Li L, Wei L, Wang Y, Han Z., Insects, 15. 2024-09-03 18:39:10.
Many insects are categorized as agricultural pests due to their ability to transmit diseases and damage crops, which results in significant economic losses. Scientists have proposed two main pest control strategies: population suppression, aimed at reducing the size or distribution of pest populations, and population replacement, which involves introducing genetically modified populations to replace wild pests after an initial release. Typically, population replacement strategies use gene drive systems to spread beneficial traits throughout the target population. Current promising gene drive systems include homing endonuclease genes (HEGs), Wolbachia, maternal-effect dominant embryonic arrest (Medea), and newly adapted CRISPR/Cas genome editing systems. This review provides an overview of the recent advancements in population replacement, including insights into the development, testing, and safe implementation of CRISPR-Cas-based gene drive techniques from laboratory settings to field applications. It also discusses recent developments, identifies research gaps, and offers a comprehensive analysis of genetic control strategies for insect pests.
Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems
31181Sally Adams; Andre Pires-daSilva, Biochemical Society Transactions, 2024-08-25 20:35:26.
The non-Mendelian transmission of sex chromosomes during gametogenesis carries significant implications, influencing sex ratios and shaping evolutionary dynamics. Here we focus on known mechanisms that drive non-Mendelian inheritance of X chromosomes during spermatogenesis and their impact on population dynamics in species with different breeding systems. In Drosophila and mice, X-linked drivers targeting Y-bearing sperm for elimination or limiting their fitness, tend to confer unfavourable effects, prompting the evolution of suppressors to mitigate their impact. This leads to a complex ongoing evolutionary arms race to maintain an equal balance of males and females. However, in certain insects and nematodes with XX/X0 sex determination, the preferential production of X-bearing sperm through atypical meiosis yields wild-type populations with highly skewed sex ratios, suggesting non-Mendelian transmission of the X may offer selective advantages in these species. Indeed, models suggest X-meiotic drivers could bolster population size and persistence under certain conditions, challenging the conventional view of their detrimental effects. Furthering our understanding of the diverse mechanisms and evolutionary consequences of non-Mendelian transmission of X chromosomes will provide insights into genetic inheritance, sex determination, and population dynamics, with implications for fundamental research and practical applications.
Mark–Release–Recapture (MRR) of Sterile Male Aedes albopictus (Skuse) in Sri Lanka: Field Performance of Sterile Males and Estimation of the Wild Mosquito Population Density
30876Hapugoda, Menaka, Nilmini Silva Gunawardena, Tharaka Ranathunge, Jeremy Bouyer, Hamidou Maiga, Kankanige Karunathilake, Gayan Parakrama Withanage, Indika Weerasinghe, Bazoumana B. D. Sow, and Jeevanie Harishchandra, Insects, 15:466. 2024-07-02 13:27:59.
Dengue is an important mosquito-borne disease in Sri Lanka. The Sterile Insect Technique (SIT) is an environment-friendly and novel method that can suppress dengue vector mosquitoes in Sri Lanka. This study aimed to evaluate the field performance of sterile males and the density of wild male Aedes albopictus (Skuse) using a Mark–Release–Recapture (MRR) assay. Laboratory-colonized male pupae were exposed to 50 Gy gamma using a Co60 source. Sterile males (approx. 10,000) marked with fluorescent dust were released weekly for 4 consecutive weeks (January–February 2021) in a geographically isolated 30 ha site in Gampaha. Results show sterile males could disperse up to 543.8 m with a mean distance of 255.1 ± 44.6 m and survive up to 6 days with a mean life expectancy of 3.55 ± 2.32 days. A high field mating competitiveness of sterile males based on a Fried value of 0.47 ± 0.007 and significant induced sterility in the wild eggs in the second generation were found. The mean wild male mosquito population density was 163 males/ha. The data generated will be useful for designing future trials in Sri Lanka and other countries with similar situations.
Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes
29563Jose L. Orozco-Gonzales, Antone dos Santos Benedito, Daiver Cardona-Salgado et al., Mathematical Biosciences, 372. 2024-04-25 17:59:21.
This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model’s parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures.
Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails
29102Michelle L. Johnson, Bruce A. Hay, Maciej Maselko, Nature Communications, 15. 2024-04-16 09:23:41.
Population-scale genome editing can be used to alter the composition or fate of wild populations. One approach to achieving these aims utilizes a synthetic gene drive element—a multi-gene cassette—to bring about an increase in the frequency of an existing allele. However, the use of gene drives is complicated by the multiple scientific, regulatory, and social issues associated with transgene persistence and gene flow. Alternatives in which transgenes are not driven could potentially avoid some of these issues. Here we propose an approach to population scale gene editing using a system we refer to as an Allele Sail. An Allele Sail consists of a genome editor (the Wind) that introduces DNA sequence edits (the Sail) at one or more sites, resulting in progeny that are viable and fertile. The editor, such as a sequence-specific nuclease, or a prime- or base-editor, is inherited in a Mendelian fashion. Meanwhile, the edits it creates experience an arithmetic, Super-Mendelian increase in frequency. We explore this system using agent-based modeling, and identify contexts in which a single, low frequency release of an editor brings edits to a very high frequency. We also identify conditions in which manipulation of sex determination can be used to bring about population suppression. Current regulatory frameworks often distinguish between transgenics as genetically modified organisms (GMOs), and their edited non-transgenic progeny as non-GMO. In this context an Allele Sail provides a path to alter traits and fates of wild populations in ways that may be considered more acceptable.
Talking About Gene Drive in Uganda: The Need for Science Communication to Underpin Engagement
29082Hartley, S., Stelmach, A., Opesen, C., Openjuru, G. L., and Neema, S., Science Communication, 2024-04-04 09:15:22.
Uganda may host the world’s first field trials of gene drive mosquitoes for malaria control. Global North discourses pre-suppose African publics have access to information about gene drive and are ready to make decisions about its governance. We explore assumptions about the availability of this information in Uganda. We find a paucity of information available combined with a strong desire for information from lay publics. We discuss these findings in the context of Ugandan information infrastructures and political sensitivities to genetic technologies. If Ugandans are to decide about gene drive, they need independent information about the science to underpin engagement.
The organizational structure of global gene drive research
29047Florian Rabitz, Global Environmental Change, 84. 2024-03-19 18:00:17.
Gene drives are a proposed method for large-scale in situ genetic engineering.
Effectiveness evaluation of mosquito suppression strategies on dengue transmission under changing temperature and precipitation
28984Kaihui Liu, Shuanghui Fang, Qiong Li, et al., Acta Tropica, 2024-03-05 20:16:41.
Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore
28940Jue Tao Lim, Somya Bansal*, Chee Seng Chong*, Borame Dickens, Youming Ng, Lu Deng, Caleb Lee, Li Yun Tan, Grace Chain, Pei Ma, Shuzhen Sim, Cheong Huat Tan, Alex R Cook, Lee Ching Ng, The Lancet Microbe, 2024-02-27 18:18:52.
Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81–78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092–2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites.
Meiotic drive against chromosome fusions in butterfly hybrids
28892Jesper Boman, Christer Wiklund, Roger Vila, Niclas Backström, bioRxiv, 2024-02-13 21:18:38.
Species frequently differ in karyotype, but heterokaryotypic individuals may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can thus serve as a mechanism for speciation between incipient lineages but their evolution poses a paradox. How does underdominant rearrangements evolve? One solution is the fixation of underdominant chromosomal rearrangements through genetic drift. However, this requires small and isolated populations. Fixation is more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate transmission ratio distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover a transmission bias favoring the fused state at chromosome with unknown polarization in one experiment and a transmission bias favoring the unfused state of derived fusions in both experiments. The latter result support a scenario where chromosome fusions can fix in populations despite counteracting effects of meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that this transmission bias can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why derived fusions may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.
Recombinant venom proteins in insect seminal fluid reduces female lifespan
28821Samuel J. Beach, Maciej Maselko, bioRxiv, 2024-01-23 14:49:23.
The emergence of insecticide resistance has increased the need for alternative pest management tools1,2 Numerous genetic biocontrol approaches, which involve the release of genetically modified organisms to control pest populations, are in various stages of development to provide highly targeted pest control3-7. However, all current mating-based genetic biocontrol technologies function by releasing engineered males which skew sex-ratios or reduce offspring viability in subsequent generations. This allows mated females continue to cause harm (e.g. transmit disease). Here, we demonstrate the first example of intragenerational genetic biocontrol, wherein mating with engineered males reduces female lifespan. The toxic male technique (TMT) involves the heterologous expression of insecticidal proteins within the male reproductive tract that are transferred to females via mating. We demonstrate TMT in Drosophila melanogaster males, which reduce the median lifespan of mated females by 37 - 59% compared to controls mated to wild type males. Agent-based models of Aedes aegypti predict that compared to existing genetic biocontrol technologies, even modest levels of mated female mortality could allow TMT to suppress a female population substantially faster, which is likely to result in reduced disease burdens. TMT presents a novel approach for combatting outbreaks of disease vectors and agricultural pests.
Perspectives of African stakeholders on gene drives for malaria control and elimination: a multi-country survey
28750Finda, M.F., Juma, E.O., Kahamba, N.F. et al., Malaria Journal, 22:8384. 2023-12-21 15:40:51.
Gene drive modified mosquitoes (GDMMs) have the potential to address Africa’s persistent malaria problem, but are still in early stages of development and testing. Continuous engagement of African stakeholders is crucial for successful evaluation and implementation of these technologies. The aim of this multi-country study was, therefore, to explore the insights and recommendations of key stakeholders across Africa on the potential of GDMMs for malaria control and elimination in the continent. A concurrent mixed-methods study design was used, involving a structured survey administered to 180 stakeholders in 25 countries in sub-Saharan Africa, followed by 18 in-depth discussions with selected groups and individuals. Stakeholders were drawn from academia, research and regulatory institutions, government ministries of health and environment, media and advocacy groups. Thematic content analysis was used to identify key topics from the in-depth discussions, and descriptive analysis was done to summarize information from the survey data. Despite high levels of awareness of GDMMs among the stakeholders (76.7%), there was a relatively low-level of understanding of their key attributes and potential for malaria control (28.3%). When more information about GDMMs was provided to the stakeholders, they readily discussed their insights and concerns, and offered several recommendations to ensure successful research and implementation of the technology. These included: (i) increasing relevant technical expertise within Africa, (ii) generating local evidence on safety, applicability, and effectiveness of GDMMs, and (iii) developing country-specific regulations for safe and effective governance of GDMMs. A majority of the respondents (92.9%) stated that they would support field trials or implementation of GDMMs in their respective countries. This study also identified significant misconceptions regarding the phase of GDMM testing in Africa, as several participants incorrectly asserted that GDMMs were already present in Africa, either within laboratories or released into the field. Incorporating views and recommendations of African stakeholders in the ongoing research and development of GDMMs is crucial for instilling stakeholder confidence on their potential application. These findings will enable improved planning for GDMMs in Africa as well as improved target product profiles for the technologies to maximize their potential for solving Africa’s enduring malaria challenge.
Engineering mice for female-biased progeny without impacting genetic integrity and litter size
28534Ido Yosef, Tridib Mahata, Yuhuang Chen, Hadas Bar-Joseph, Ruth Shalgi, Ariel Munitz, Motti Gerlic, Udi Qimron, bioRxiv, 2023-11-28 10:45:00.
Generating mammalian gametes with a skewed sex ratio has thus far eluded empirical confirmation. The utilization of such genetically engineered organisms would offer the potential to curtail the necessity for culling animals of undesirable sex, mitigate resource wastage, and alleviate superfluous labor burdens. In this study, we introduce a transgenic male mouse lineage, which consistently yields predominantly female progeny (comprising up to 91% of the total offspring). This accomplishment was made possible by integrating a controllable genetic cassette onto the Y chromosome. The cassette encodes dCas9 and RNA guides that selectively silence a spermatid maturation gene. After the separation of X and Y gametes during meiosis, gametes containing an X chromosome develop normally, while those harboring the engineered Y chromosome, subjected to dCas9 silencing of the spermatid maturation gene, do not mature properly. Indeed, some spermatozoa from the transgenic mice exhibit a unique morphology, associated with the absence of the maturation gene. Notably, the resultant female offspring do not inherit the genetically engineered Y chromosome and are thus not genetically modified. Importantly, the litter size of the transgenic mice remains unchanged compared to the wild type. These findings represent a groundbreaking demonstration of genetic engineering’s potential to yield sex-biased litters of full size without compromising genetic integrity, marking a pioneering advancement in this field of study.
Framing Challenges and Opportunities for Canada: Expert Panel on Regulating Gene-Edited Organisms for Pest Control
28486CCA (Council of Canadian Academies), Framing Challenges and Opportunities for Canada, 2023-11-21 11:21:00.
Gene-editing technologies are changing approaches to pest management. Rapidly evolving but unproven gene-editing tools could potentially mitigate the impacts of pests in public health, conservation, and agricultural contexts. The use of these tools, however, is accompanied by uncertainties about possible impacts on species and ecosystems, along with broader socioeconomic and cultural risks. Increased globalization and climate change are intensifying pest problems. These factors, combined with the waning effectiveness of many common pest-control tools, will contribute to growing pressure from both native and invasive pests if left unchecked. Opportunities to manage pests with greater effectiveness, lower costs, and increased safety therefore require consideration.
Transformative Novel Technologies and Global Environmental Governance
28377F. Rabitz, Cambridge University Press, 2023-11-13 09:55:21.
Transformative Novel Technologies are potential gamechangers for confronting climate change, biodiversity loss, and many other elements of the global environmental crisis, allowing us to achieve a more sustainable future. The contemporary and future international governance of these technologies has crucial implications for managing the global transition towards sustainability. This book is the first to present a comprehensive assessment of the impact of these technologies on international politics. The author examines the responses of international institutions to the emergence of these technologies, focusing on three broad domains: biotechnology, climate engineering, and mineral extraction in areas beyond national jurisdiction (the ocean floor or near-Earth asteroids). This book is aimed at a non-specialist, academic audience with interest in the international and environmental politics of sustainability and technology. This title is part of the Flip it Open Programme and may also be available Open Access. Check our website - Cambridge Core - for details.
Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
28311A. Minwuyelet, G. P. Petronio, D. Yewhalaw, A. Sciarretta, I. Magnifico, D. Nicolosi, R. Di Marco and G. Atenafu, Frontiers in Microbiology, 14. 2023-11-08 08:20:47.
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
Biotechnological Potential of Microorganisms for Mosquito Population Control and Reduction in Vector Competence
28272R. D. Katak, A. M. Cintra, B. C. Burini, O. Marinotti, J. A. Souza-Neto and E. M. Rocha, Insects, 14. 2023-10-30 07:59:35.
Mosquitoes transmit pathogens that cause human diseases such as malaria, dengue fever, chikungunya, yellow fever, Zika fever, and filariasis. Biotechnological approaches using microorganisms have a significant potential to control mosquito populations and reduce their vector competence, making them alternatives to synthetic insecticides. Ongoing research has identified many microorganisms that can be used effectively to control mosquito populations and disease transmission. However, the successful implementation of these newly proposed approaches requires a thorough understanding of the multipronged microorganism-mosquito-;pathogen-environment interactions. Although much has been achieved in discovering new entomopathogenic microorganisms, antipathogen compounds, and their mechanisms of action, only a few have been turned into viable products for mosquito control. There is a discrepancy between the number of microorganisms with the potential for the development of new insecticides and/or antipathogen products and the actual available products, highlighting the need for investments in the intersection of basic research and biotechnology.
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