Keywords: Genetic engineering
“Target species complex” concept: Strengthening environmental risk assessment of engineered gene drives
35531J.B. Connolly, Y. Devos, D.C.M. Glandorf, and J. Romeis, Proc. Natl. Acad. Sci., 2026-03-30 19:11:30.
The recent opinion piece of Christophe Boëte critiqued the concept of the target species complex (TSC) in environmental risk assessment (ERA) of engineered gene drives (EGDs) (1). While constructive debate is essential, the piece misrepresents the purpose of TSC and conflates unrelated mechanisms, creating misconceptions that merit clarification. Malaria-transmitting mosquitoes often belong to species complexes, comprising vector and nonvector species, where hybridization can be detected in laboratory settings and occasionally in the field (2–4). Low-threshold EGDs are self-sustaining and nonlocalizing (5). Should such EGD be released in a species complex where target genomic sequences are conserved, in the event of interspecific mating in the field vertical gene drive transfer (VGDT) to nonvector species could occur, potentially harming biodiversity protection goals. Conversely, VGDT to vector species could advance health objectives (6).
Stochastic dynamics at the back of a gene drive eradication wave
35468Léna Kläy, Léo Girardin, Florence Débarre, Vincent Calvez, Theoretical Population Biology, 168:44-64. 2026-02-24 14:22:40.
Gene drive alleles bias their own inheritance to offspring. They can fix in a wild-type population in spite of a fitness cost, and even lead to the eradication of the target population if the fitness cost is high. However, this outcome may be prevented or delayed if areas previously cleared by the drive are recolonised by wild-type individuals. Here, we investigate the conditions under which these stochastic wild-type recolonisation events are likely and when they are unlikely to occur in one spatial dimension. More precisely, we examine the conditions ensuring that the last individual carrying a wild-type allele is surrounded by a large enough number of drive homozygous individuals, resulting in a very low chance of wild-type recolonisation. To do so, we make a deterministic approximation of the distribution of drive alleles within the wave, and we split the distribution of wild-type alleles into a deterministic part and a stochastic part. Our analytical and numerical results suggest that the probability of wild-type recolonisation events increases with lower fitness of drive individuals and with smaller local carrying capacity. Numerical simulations show that these results extend to two spatial dimensions. The role of the migration rate however, is less clear but has a lower impact. We further demonstrate that, in the event of wild-type recolonisation, the probability of subsequent drive reinvasion decreases with smaller values of the intrinsic growth rate of the population. Overall, our study paves the way for further analysis of wild-type recolonisation at the back of eradication travelling waves.
Evaluating paratransgenesis using engineered symbiotic bacteria for Plasmodium inhibition in mosquito vectors: A systematic review
35538Cleanclay WD, Kernyuy FB, Kintung IF, et al, PLoS Neglected Tropical Diseases, 2026-02-12 16:54:19.
Malaria is one of the key world health problems, especially in sub-Saharan Africa, where the rising resistance to insecticides and antimalarial drugs is posing a threat to the current control mechanisms. New strategies are urgently needed to break the cycle of the spread of Plasmodium parasites by the Anopheles mosquito. A potential solution is paratransgenesis, which involves the genetic modification of naturally occurring mosquito-associated microbes to produce molecules that prevent the development of parasites in the gut of the mosquito. In this systematic review, we examined experimental studies that investigated paratransgenesis as a malaria control measure. Using the PRISMA guideline, we identified ten eligible studies that had engineered bacterial or fungal symbionts to express antiplasmodial effector proteins. These studies showed that feeding mosquitoes a sugar meal containing engineered microbes resulted in a stable colonization of the mosquito midgut. Several of the molecules tested were highly effective in reducing parasite development, with scorpine consistently showing strong transmission-blocking activity, achieving parasite inhibition rates greater than 90% in different experimental systems. Inhibitory effects were also further augmented by the combination of several effector molecules. Overall, the finding suggests that paratransgenesis has strong potential as an additional malaria control measure. Nevertheless, contests concerning ecological safety, microbial stability, and field implementation will need to be solved before large-scale implementation can be done.
A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population
35426Kaduwal, S., Stuart, E.C., Auradkar, A. et al., npj Antimicrobials and Resistance, 4. 2026-02-05 10:30:00.
Antibiotic resistance (AR) is an escalating public health threat, necessitating innovative strategies to control resistant bacterial populations. One promising approach involves engineering genetic elements that can spread within microbial communities to eliminate AR genes. Previously, we developed Pro-Active Genetics (Pro-AG), a CRISPR-based gene-drive-like system capable of reducing AR colony-forming units (CFU) by approximately five logs. Here, we advance this technology by integrating Pro-AG into a conjugative transfer system, enabling efficient dissemination of an anti-AR gene cassette between two bacterial strains. Additionally, we characterize a complementary homology-based deletion (HBD) process, a CRISPR-driven mechanism that precisely removes target DNA sequences flanked by short direct repeats. Our findings reveal that Pro-AG and HBD are differentially influenced by the bacterial RecA pathway and that HBD components can be delivered via plasmids or phages to selectively delete Pro-AG cassettes. This built-in safeguard prevents uncontrolled spread of a gene cassette and mitigates unanticipated side effects. These refinements enhance the efficiency and flexibility of Pro-AG, expanding its potential applications in microbiome engineering, environmental remediation, and clinical interventions aimed at combating antibiotic resistance. More broadly, this work establishes a proof-of-principle for microbiome engineering strategies that could be leveraged to improve health and restore ecological balance.
Genetically modified mice could fight Lyme disease in Massachusetts
35429Dave Puglisi, 7News, 2026-01-29 10:43:05.
Tiny insects are spreading a devastating disease. Scientists at Massachusetts Institute of Technology (MIT) believe they’ve discovered something that could help stop Lyme disease before it starts. “The right side of my body went numb. I felt disoriented. My heart was racing,” said Brandi Dean. Dean thought what she was experiencing was a stroke but it was actually the start of a 10-year battle with Lyme disease. “It’s a devastating illness, emotionally, physically, and financially,” she said. The illness began with a tick bite that spread bacteria throughout her body. “I was really struggling to just survive every day and to take care of my kids,” said Dean. Brandi pushed through muscle pain, dizziness and exhaustion so severe she couldn’t walk down the stairs. “I would literally scoot down each stair. I had very little energy to walk,” said Dean. “It was frightening at that time.” Doctor Sam Telford, a professor of infectious disease and global health at Tufts University, has studied ticks for more than 40-years. He says mice are a perfect host for several diseases ticks can spread. “They’re very good hosts for the bacteria. They suffer no disease from having the bacteria,” said Telford. “They pass it back-and-forth and us humans are collateral damage.”
Gene drives, species complexes, and the risks of collateral damage
35296C. Boëte, Proc. Natl. Acad. Sci., 122. 2025-11-09 18:26:26.
The development of engineered gene drive systems continues to garner significant interest. Theoretically, these systems could spread traits in a target species (an approach known as population replacement) or eliminate a population within a few generations (population suppression). Some researchers have promoted this disruptive technology for potential applications ranging from public health (e.g., malaria control) to conservation (e.g., protection of endangered species, elimination of invasive ones) to agriculture (e.g., pest control). But in the case of a gene drive intended to target a specific species, the risk of affecting non-target species must be taken into account, and researchers must strive to minimize collateral damage. Hybridization between a target and a non-target species could result in unintended gene flow, as could the horizontal transfer of the gene drive cassette (1). While some researchers have proposed the “Target Species Complex” (TSC) framework to account for off-target effects, the concept is unlikely to provide a safeguard. Rather, it risks reframing collateral impacts as intentional outcomes, narrowing, rather than broadening, the scope of ecological and regulatory considerations. Researchers must therefore make sure to incorporate risk assessments that take into account the effects on numerous species and make a concerted effort to understand the downstream effects.
Reactions as IUCN Congress votes to adopt Policy on Synthetic Biology, rejects genetic engineering moratorium
35245EnvironNews Nigeria, 2025-10-15 09:12:00.
Following the vote at the IUCN World Conservation Congress, members have rejected a moratorium on genetic engineering of wild species (Motion 133) and adopted the IUCN Policy on Synthetic Biology (Motion 087), a move observers see as a signal of support for a science-based, case-by-case approach to innovation in conservation. The Outreach Network for Gene Drive Research has welcomed the outcome as a vote of confidence in scientific collaboration and evidence-led policymaking. In a statement, the Outreach Network for Gene Drive Research said: “As a coalition that champions the value of responsible research, we welcome the adoption of IUCN’s Policy on Synthetic Biology as a constructive, balanced and science-based approach towards the potential application of this emerging field for conservation. “The escalating biodiversity crisis poses a grave threat to the future of all life on earth, with more than a million species at risk of extinction. Synthetic biology, including genetic engineering, offers new hope for solutions that can rise to the scale and urgency of the challenge.
Exploring experts’ uncertainties about gene drive technology for agricultural pest control in the U.S.: a qualitative study to inform innovation and decision-making
35241Barry, N., Barnhill, S.K. & Johnson, B.B., Environment Systems and Decisions, 45. 2025-10-15 08:34:10.
As experts consider what it might look like for gene drives to manage agricultural pests, there remain several uncertainties across a broad range of issues, including technical, ecological, regulatory, and social implications. Drawing on 25 expert interviews, we parse out these uncertainties and the potential for Adaptive Management to help guide development, deployment, and governance of gene drives for invasive agricultural pest management. Adaptive Management emerged specifically to attend to uncertainties in complex social-ecological systems, prescribing collective learning and responsiveness to stakeholder feedback to effectively reach management goals. Thus, Adaptive Management provides clear direction on how to account for and make decisions in the face of considerable uncertainties surrounding these gene drive tools. We also give some attention to the ways in which the uncertainties that are specific to agricultural applications are somewhat distinct from or consistent with global discourse around gene drive development across sectors.
Genetically engineered mice could take the bite out of Lyme disease on Nantucket, scientists say
35149Jon LaPook, Denise Schrier Cetta, Aliza Chasan, Katie Brennan, CBS News, 2025-09-21 10:07:27.
Over the past 40 years, Dr. Timothy Lepore has been the emergency room head, sole surgeon and medical examiner on Nantucket, a small island off Cape Cod, Massachusetts. Today he runs the only private practice, where he treats dozens of patients with Lyme disease each year. About 15% of residents on the island have been afflicted with the disease, which can cause a wide range of symptoms like a fever, rash, facial paralysis, an irregular heartbeat and arthritis. Lepore, 80, may finally be able to retire if a team of scientists' dream to curb the transmission of Lyme disease on the island becomes a reality. The scientists' target is not the deer or ticks often associated with the disease: it's wild mice, the main host of Lyme bacteria. The hope is that by genetically engineering mice to be immune to Lyme and releasing them in Nantucket, the population of mice able to spread Lyme disease on the island will shrink. The problem on Nantucket can be traced back to 1926, when the community voted to import two female deer to the island to give a lone buck company. On top of that, by the 1950s, half the land on the island was put into conservation. The untamed brush and wild grasslands create an ideal ecosystem for Lyme's hosts to thrive. As the deer population grew, so did the population of ticks. Deer don't get Lyme, but female ticks feed on them, and then lay as many as 2,000 eggs in a single batch. Deer also spread the disease as thousands of them carry ticks across Nantucket. Not all ticks carry Lyme disease, and a tick bite doesn't guarantee the transmission. Even if the tick is carrying Lyme, the tick has to be attached for more than 24 hours to infect someone.
Engagement for genetic modification technologies in conservation: For whom, how, and for what ends?
35126Sylvia Nissen, Franca A. Buelow, Riley Taitingfong, Amanda Black, Environmental Science & Policy, 171. 2025-09-09 09:15:42.
Questions of engagement loom large for the use of genetic modification technologies in conservation. As scientific teams rapidly move towards implementing changes that will fundamentally alter entire species, concerns are regularly raised that associated engagement activities are inadequate. It is therefore vital to take stock of recent social research that critically examines how engagement is being enacted: who is engaged and by whom, how and on what terms, and for whom or what those processes serve. Despite a rise in calls for engagement, our review shows emergent gestures towards engagement by developers and regulators lean strongly towards narrow instrumental approaches that reinforce knowledge hierarchies and existing power imbalances. It contributes to engagement practices that are often vague and tokenistic, and focused on one-way education and snapshots of opinion, rather than mutual reciprocity and dialogue. To counter these undercurrents, our review draws attention to the ways social researchers are seeking to reorient engagement for genetic modification towards its more substantive and democratic possibilities, through articulating process, amplifying plurality, and acknowledging contestation.
Field Performance of a Self-Limiting, Genetically Engineered Fall Armyworm for Biological Pest Management
35180Reavey Catherine E. , Domingues Felipe A. , Ercit Kyla, et al., Sec. Pest Management, 7. 2025-08-21 14:28:43.
The fall armyworm is one of the most globally significant agricultural pests, damaging corn, sorghum and other crops central to food production. It has developed resistance to several classes of chemical insecticides and, more recently, insect-resistant ‘Bt’ biotech corn varieties. As Bt varieties constitute the great majority of corn acreage in Brazil, proactive resistance management strategies are required to protect the durability of insecticidal efficacy of those cultivars. Previously, we reported on the development of a ‘self-limiting’ fall armyworm strain, called OX5382G, which – after release in the field – is engineered to suppress populations of fall armyworm and manage resistance to Bt crops in treated populations of this pest. Here, we build on this work by carrying out contained studies to empirically assess the pest suppression and resistance management benefits of releasing OX5382G males. We also report on the first open field releases of the OX5382G self-limiting strain in Brazil. Following commercial biosafety approval of this strain by Brazilian government regulators, deployment-relevant OX5382G male performance was then assessed in larger, operational trials in Brazil. Pest suppression and resistance management benefits were demonstrated in contained studies. In the first open field releases, OX5382G males showed comparable performance with wild-type counterparts in terms of dispersal and mating ability. In the subsequent larger, farm-scale trials in Brazil, OX5382G mated effectively in the field and we demonstrated that relatively modest release rates can achieve over-flooding ratios expected to exert suppression and/or resistance management. All assessments to date suggest that self-limiting fall armyworm is a promising future tool for managing fall armyworm and extending the durability of Bt crops’ effectiveness against damaging lepidopteran pests.
CRISPR-GPT for agentic automation of gene-editing experiments
35077Qu, Y., Huang, K., Yin, M. et al., Nat. Biomed. Eng, 2025-07-30 12:34:29.
Performing effective gene-editing experiments requires a deep understanding of both the CRISPR technology and the biological system involved. Meanwhile, despite their versatility and promise, large language models (LLMs) often lack domain-specific knowledge and struggle to accurately solve biological design problems. We present CRISPR-GPT, an LLM agent system to automate and enhance CRISPR-based gene-editing design and data analysis. CRISPR-GPT leverages the reasoning capabilities of LLMs for complex task decomposition, decision-making and interactive human–artificial intelligence (AI) collaboration. This system incorporates domain expertise, retrieval techniques, external tools and a specialized LLM fine tuned with open-forum discussions among scientists. CRISPR-GPT assists users in selecting CRISPR systems, experiment planning, designing guide RNAs, choosing delivery methods, drafting protocols, designing assays and analysing data. We showcase the potential of CRISPR-GPT by knocking out four genes with CRISPR-Cas12a in a human lung adenocarcinoma cell line and epigenetically activating two genes using CRISPR-dCas9 in a human melanoma cell line. CRISPR-GPT enables fully AI-guided gene-editing experiment design and analysis across different modalities, validating its effectiveness as an AI co-pilot in genome engineering.
Driving a protective allele of the mosquito FREP1 gene to combat malaria
34980Li, Z., Dong, Y., You, L. et al., Nature, 2025-07-24 09:46:46.
Malaria remains a substantial global health challenge, causing approximately half a million deaths each year1. The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium2. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito3. Here we generate congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.
Unlocking Gene Drive in Agriculture
34897Sarah Lee, Number Analytics, 2025-06-06 08:31:38.
Gene drive is a revolutionary genetic engineering technique that has the potential to transform the field of agricultural biotechnology. In this section, we will explore the definition, mechanism, and history of gene drive technology, as well as its potential applications in agriculture. Gene drive is a naturally occurring phenomenon where a particular gene or set of genes is inherited at a higher rate than expected under normal Mendelian inheritance. This is achieved through the use of CRISPR-Cas9 genome editing technology, which enables scientists to selectively modify genes and drive them through a population at an exponential rate. The mechanism of gene drive involves the following steps: Target gene identification: Scientists identify a target gene that they want to drive through a population. CRISPR-Cas9 editing: The CRISPR-Cas9 system is used to edit the target gene and introduce a gene drive element. Gene drive inheritance: The gene drive element is inherited by offspring at a higher rate than expected, leading to the spread of the modified gene through the population.
Screwworm Fly: US Threat & Prevention
34883News Directory 3, 2025-06-02 18:43:27.
A resurgence of the New World screwworm, a parasite known for consuming living flesh, is raising alarms in the U.S.cattle industry. For seven decades, the United States has waged an aerial war against this pest, scientifically known as C.hominivorax, which targets livestock and even humans. The U.S.Department of Agriculture (USDA) pioneered a strategy in the 1950s involving the mass production, sterilization via radiation, and aerial release of sterile screwworms to disrupt the parasite’s reproduction cycle. This approach successfully created a barrier at the Darién Gap between Panama and Colombia, effectively shielding North America. However, in 2022, this barrier was breached. Panama saw a surge in screwworm cases, and by 2024, the parasite was rapidly advancing northward.It has now reached Oaxaca and Veracruz in Mexico, prompting the U.S. to suspend live-cattle imports from Mexico. Wayne Cockrell,a Texas rancher and chair of the cattle-health committee for the Texas and Southwestern Cattle Raisers Association, expressed concern about the potential return of the screwworm to Texas. He believes the current sterile-fly programme lacks the capacity to contain the outbreak.
Assessing the population genetic structure and demographic history of Anopheles gambiae and An. arabiensis at island and mainland populations in Uganda: Implications for testing novel malaria vector control approaches
34868Rita Mwima, Tin-Yu J. Hui, Edward Lukyamuzi, et al, bioRxiv, 2025-05-26 21:26:56.
This study collected 2918 Anopheles gambiae and 173 Anopheles. arabiensis across six populations from both the islands on Lake Victoria and mainland Uganda for amplicon sequencing. Large pairwise FST values were observed between the two species, indicating their divergence. We observed low but often significant FST values between the 6 An. gambiae populations, while between the An. arabiensis mainland populations, FST values were not significant. Principal Component Analysis also revealed strong genetic structure between the two species but did not provide a clear picture between populations within each species. We also found that mainland An. gambiae populations had higher within population genetic diversity than the islands’, while An. arabiensis had the lowest nucleotide diversity. Tajima’s D values were all negative, suggesting a recent population expansion. The islands An. gambiae populations had very low contemporary effective population sizes in the tens and hundreds, as estimated from linkage disequilibrium, while the mainland population sizes were consistently higher, in the thousands.
Gene drive: communication, hype, and the publics
34577Boëte, C., Journal of Medical Entomology, 2025-03-12 16:35:04.
Engineered gene drive (EGD) systems are probably the most high-tech approach considered for their potential role in the control of vector-borne diseases. Interestingly, the rhetoric around it often goes along with a negative presentation of the current “conventional” tools and exaggerated promises about EGD themselves, leading to a situation of hype.
Establishment of pupal color as a screening marker and activity analysis of six U6 promoters in Zeugodacus cucurbitae using the white pupae gene
34487Fan Z., Wu Y., Zha X., Ma S., et al., Pest Management Science, 2025-02-04 17:36:39.
The genetic control method, which is environmentally friendly and species-specific, has effectively reduced or eliminated pests in many areas. One essential requirement to control a species is the identification of its genetic and molecular elements. Such elements, however, are rarely available in Zeugodacus cucurbitae, a very destructive insect pest worldwide. In this study, we knocked out the white pupae (wp) gene in Z. cucurbitae and generated a wp(−) strain, which has a white pupae phenotype. The white puparium color was successfully restored to brown by inserting the wp gene rescue allele into the genome of the wp(−) strain using piggyBac transgenic technology. The potential wp promoter was then truncated to drive the expression of the wp gene and the puparium color was rescued even by the 605 bp sequence upstream of its transcription initiation site. Further fertility tests showed that knocking out or rescuing the wp gene had no effect on the reproduction of adult flies. In addition, we identified six U6 promoters and tested their promoter activities in the embryos of Z. cucurbitae. The ZcU6-2 and ZcU6-1 promoters exhibited significantly higher activity than the others and are suitable for use in CRISPR technology-based genetic control methods. Our work first shows the success of applying piggyBac transgenic technology in Z. cucurbitae. Our results demonstrate a highly efficient transgenic screening marker by puparium color and the promoter activity of multiple ZcU6 promoters, facilitating the construction of transgenic strains that are used for genetic control of tephritid species. © 2025 Society of Chemical Industry.
Gene drive-based population suppression in the malaria vector Anopheles stephensi
34372Xu, X., Chen, J., Wang, Y. et al., Nature Communications, 16:1007. 2025-01-28 14:41:08.
Gene drives are alleles that can bias the inheritance of specific traits in target populations for the purpose of modification or suppression. Here, we construct a homing suppression drive in the major urban malaria vector Anopheles stephensi targeting the female-specific exon of doublesex, incorporating two gRNAs and a nanos-Cas9 to reduce functional resistance and improve female heterozygote fitness. Our results show that the drive was recessive sterile in both females and males, with various intersex phenotypes in drive homozygotes. Both male and female drive heterozygotes show only moderate drive conversion, indicating that the nanos promoter has lower activity in A. stephensi than in Anopheles gambiae. By amplicon sequencing, we detect a very low level of resistance allele formation. Combination of the homing suppression drive and a vasa-Cas9 line boosts the drive conversion rate of the homing drive to 100%, suggesting the use of similar systems for population suppression in a continuous release strategy with a lower release rate than SIT or fsRIDL techniques. This study contributes valuable insights to the development of more efficient and environmentally friendly pest control tools aimed at disrupting disease transmission.
A comprehensive review of biological and genetic control approaches for leishmaniasis vector sand flies; emphasis towards promoting tools for integrated vector management
34611Kumari, Y., Gunathilaka, N., Amarasinghe, D., PLOS Neglected Tropical Diseases, 19. 2025-01-27 11:07:43.
Leishmaniasis is a health problem in many regions with poor health and poor life resources. According to the World Health Organization (WHO), an estimated 700,000–1 million new cases arise annually. Effective control of sand fly vector populations is crucial for reducing the transmission of this disease. Therefore, this review aims to comprehensively examine and evaluate the current methods for controlling sand fly populations, focusing on biological and gene drive techniques. A detailed, comprehensive literature search was carried out using databases including Google Scholar, PubMed, ScienceDirect, and the National Library of Medicine (NIH). These searches were done using specific keywords related to the field of study. This current review identified several promising methods, including genetically modified sand flies, using transgenic approaches by taking advanced gene editing tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) and genetic modification of symbiotic microorganisms for controlling sand fly populations, which appeared to be proven under laboratory and field settings. Genetic control approaches have many benefits over chemical control, including long-lasting effects on targets, high specificity, and less environmental impact. Advances in genetic engineering technologies, particularly CRISPR/Cas9, sterile insect techniques, and gene drive insect modification, offer new avenues for precise and efficient sand fly management. Future research should prioritize optimizing rearing and sterilization techniques, conducting controlled field trials, and fostering collaboration across disciplines to realize the potential of genetic control strategies in combating leishmaniasis.
‘Toxic Male Technique’ promises faster biocontrol of mosquito populations
34223Macquarie University, Phys.org, 2025-01-07 20:57:52.
A new biological pest control method that targets the lifespan of female insects could significantly reduce the threat of insect pests such as disease-carrying mosquitoes by offering faster and more effective results than current methods. Described in Nature Communications, the technique developed by researchers in Applied BioSciences and the ARC Center of Excellence in Synthetic Biology at Macquarie University is a new approach called the Toxic Male Technique (TMT). It works by genetically engineering male insects to produce insect-specific venom proteins in their semen. When these males mate with females, the proteins are transferred, significantly reducing female lifespan and their ability to spread disease. Insect pests pose a growing threat to global health and agriculture, causing hundreds of thousands of deaths, millions of infections, and costing billions in health care and crop damage annually. In mosquitoes like Aedes aegypti and Anopheles gambiae, only the females bite and transmit diseases such as malaria, dengue, Zika, chikungunya disease and yellow fever. Pesticides face declining effectiveness due to resistance and have caused harm to non-target species and ecosystems. Genetic biocontrol has emerged as a promising alternative. Current techniques like the Sterile Insect Technique (SIT) or insects carrying lethal genes (RIDL) work by releasing massive numbers of sterilized or genetically modified males to mate with the wild females. While these mated females produce no offspring or only male offspring, they continue to blood-feed and spread disease until they die naturally—meaning populations of biting females only decrease when the next generation emerges. By immediately reducing the biting female population, TMT offers significant advantages over competing genetic biocontrol methods. "As we've learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics," says lead author Sam Beach.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
34215Tolosana, I., Willis, K., Gribble, M. et al., Nature Communications, 16:206. 2025-01-07 09:21:41.
Genetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.
Improving the suppressive power of homing gene drive by co-targeting a distant-site female fertility gene
33386Faber, N.R., Xu, X., Chen, J. et al., Nature Communications, 15. 2024-11-04 17:07:21.
Gene drive technology has the potential to address major biological challenges. Well-studied homing suppression drives have been shown to be highly efficient in Anopheles mosquitoes, but for other organisms, lower rates of drive conversion prevent elimination of the target population. To tackle this issue, we propose a gene drive design that has two targets: a drive homing site where drive conversion takes place, and a distant site where cleavage induces population suppression. We model this design and find that the two-target system allows suppression to occur over a much wider range of drive conversion efficiency. Specifically, the cutting efficiency now determines the suppressive power of the drive, rather than the conversion efficiency as in standard suppression drives. We construct a two-target drive in Drosophila melanogaster and show that both components of the gene drive function successfully. However, cleavage in the embryo from maternal deposition as well as fitness costs in female drive heterozygotes both remain significant challenges for both two-target and standard suppression drives. Overall, our improved gene drive design has the potential to ease problems associated with homing suppression gene drives for many species where drive conversion is less efficient.
Navigating biosafety regulatory frameworks for genetic engineering in Africa: a focus on genome editing and gene drive technologies
33383Tilahun Rabuma, Felix Moronta-Barrios, Wendy Craig, Frontiers in Bioengineering and Biotechnology, 12. 2024-11-04 16:05:02.
Genome editing and gene drive technologies are increasingly gaining attraction in Africa, with researchers exploring their potential applications in agriculture, health and the environment. Acknowledging that robust regulatory frameworks are crucial in facilitating the development and utilization of these technologies, informed decision-making is, however, being impeded by the fragmented information availability and readiness of regulatory authorities on the continent. This study investigates the regulatory frameworks governing genome editing and gene drive technologies in African countries, identifies common regulatory challenges and proposes actionable solutions. Primary data were collected through questionnaires and complemented by analyzing existing biosafety regulations from online databases and scientific literature. Our findings suggest that while a few African countries have recently updated their regulatory frameworks, many are still under discussion. Challenges to development and implementation include limited resources, expertise, awareness, and public resistance. The findings underscore the urgent need for further development in regulatory capacities. By shedding light on these challenges, our study could provide African regulators with valuable insights to guide the formulation of effective regulatory frameworks. Such frameworks are essential for harnessing the potential of genome editing and gene drive technologies while safeguarding human health and the environment in Africa.
Exploring The Dynamics of Gene Drive Mosquitoes Within Wild Populations Using an Agent-Based Simulation
34602S. Wickramasooriya, I. Mahmood, A. Calinescu, M. Wooldridge and G. Lanzaro, 2024 Annual Modeling and Simulation Conference, Washington, D.C.:1-14. 2024-10-29 10:38:49.
Gene drive technology is emerging as a potentially powerful tool in combating vector-borne diseases – notably malaria. This study introduces an agent-based model (ABM) focused on the deployment of genetically engineered mosquitoes with gene drive (GEM) in Príncipe Island, Republic of São Tomé and Príncipe, an island nation in the Gulf of Guinea, West Africa. Grounded in empirical data from laboratory and field studies, our model forecasts the dynamics of mosquito populations central to devising efficacious GEM release strategies. The core objective is to evaluate the time required for GEMs to constitute 90% of the mosquito population and to elucidate their dispersal throughout the island. This research is instrumental in understanding GEM potential in controlling malaria vectors.
Gene Drives: A Powerful and Controversial Genetic Technology
31456Biomedical and Life Sciences Simplified, YouTube, 2024-09-03 09:01:56.
Gene drives represent a powerful yet controversial genetic technique that challenges traditional Mendelian inheritance. By introducing self-propagating changes into an organism's genome, gene drives can ensure that a specific mutation becomes homozygous in offspring, effectively spreading it through a population. This powerful tool has potential applications in eradicating mosquito-borne diseases like malaria and Zika, combating drug-resistant pathogens, and controlling invasive species. But how exactly does it work? This video breaks down the science behind gene drives and the role of CRISPR technology.
Teosinte Pollen Drive guides maize diversification and domestication by RNAi
34650Berube, B., Ernst, E., Cahn, J. et al., Nature, 633:380-388. 2024-08-07 06:59:44.
Selfish genetic elements contribute to hybrid incompatibility and bias or ‘drive’ their own transmission1,2. Chromosomal drive typically functions in asymmetric female meiosis, whereas gene drive is normally post-meiotic and typically found in males. Here, using single-molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Z. mays ssp. mexicana) that depends on RNA interference (RNAi). 22-nucleotide small RNAs from a non-coding RNA hairpin in mexicana depend on Dicer-like 2 (Dcl2) and target Teosinte Drive Responder 1 (Tdr1), which encodes a lipase required for pollen viability. Dcl2, Tdr1 and the hairpin are in tight pseudolinkage on chromosome 5, but only when transmitted through the male. Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas3, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize4. A survey of maize traditional varieties and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least four chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive probably had a major role in maize domestication and diversification, and offers an explanation for the widespread abundance of ‘self’ small RNAs in the germ lines of plants and animals.
An egg-sabotaging mechanism drives non-Mendelian transmission in mice
31028Frances E. Clark, Naomi L. Greenberg, Duilio M.Z.A. Silva, et al, Current Biology, 2024-08-05 11:40:23.
Selfish genetic elements drive in meiosis to distort their transmission ratio and increase their representation in gametes, violating Mendel’s law of segregation. The two established paradigms for meiotic drive, gamete killing and biased segregation, are fundamentally different. In gamete killing, typically observed with male meiosis, selfish elements sabotage gametes that do not contain them. By contrast, killing is predetermined in female meiosis, and selfish elements bias their segregation to the single surviving gamete (i.e., the egg in animal meiosis). Here, we show that a selfish element on mouse chromosome 2, Responder to drive 2 (R2d2), drives using a hybrid mechanism in female meiosis, incorporating elements of both killing and biased segregation. We propose that if R2d2 is destined for the polar body, it manipulates segregation to sabotage the egg by causing aneuploidy, which is subsequently lethal in the embryo, ensuring that surviving progeny preferentially contain R2d2. In heterozygous females, R2d2 orients randomly on the metaphase spindle but lags during anaphase and preferentially remains in the egg, regardless of its initial orientation. Thus, the egg genotype is either euploid with R2d2 or aneuploid with both homologs of chromosome 2, with only the former generating viable embryos. Consistent with this model, R2d2 heterozygous females produce eggs with increased aneuploidy for chromosome 2, increased embryonic lethality, and increased transmission of R2d2. In contrast to typical gamete killing of sisters produced as daughter cells in a single meiosis, R2d2 prevents production of any viable gametes from meiotic divisions in which it should have been excluded from the egg.
Germline Cas9 promoters with improved performance for homing gene drive
30488Du, J., Chen, W., Jia, X. et al., Nature Communications, 15:4560. 2024-06-04 16:50:42.
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type alleles into drive alleles in heterozygotes with Cas9 and gRNA. It is thus desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we test eleven Drosophila melanogaster germline promoters. Some achieve higher drive conversion efficiency with minimal embryo resistance, but none completely avoid somatic expression. However, such somatic expression often does not carry detectable fitness costs for a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Supporting a 4-gRNA suppression drive, one promoter leads to a low drive equilibrium frequency due to fitness costs from somatic expression, but the other outperforms nanos, resulting in successful suppression of the cage population. Overall, these Cas9 promoters hold advantages for homing drives in Drosophila species and may possess valuable homologs in other organisms.
CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males
28970Smidler, A.L., Marrogi, E., Kauffman, J. et al., Scientific Reports, 14. 2024-03-05 13:54:40.
Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
28802Meccariello, A., Hou, S., Davydova, S. et al., Nature Communications, 15:372. 2024-01-15 17:13:20.
Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medfly transformer gene, we also demonstrate how CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.
Viruses that ‘infect’ viruses: Cas12f1 and Cas9 gene drive in HSV1
28673Hongsheng Dai, Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianyin Zeng, Guangxiong Lei, Tongwen Zhang, bioRxiv, 2023-12-06 12:08:32.
Cas9-based synthetic gene drives constitute some minimal elements capable of editing DNA with sequence specificity. However, they face high resistance rate and mitigation strategies developed so far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses carrying either Cas9 or Cas12f1 gene drives, and compared their performance in spreading the gene drive and causing resistance. Based on phenotypical staining and NGS sequencing, we showed that HSV1 supported fast and effective transmission of gene drive, and Cas12f1 gene drive yielded higher conversion and lower resistance than Cas9 gene drive. Cas12f1 gene drive is a promising alternative to Cas9 gene drive, and HSV1 is a reliable and fast platform to evaluate gene drive. Gene drive viruses worked like pathogens that specifically infect viruses and could potentially be used to attenuate viral infection.
Homing-based gene drives can introgress rapidly into local genetic backgrounds with minimal chromosomal conversion in Anopheles gambiae
28663Tony Nolan, Poppy Pescod, Giulia Bevivino et al., Research Square, 2023-12-06 10:02:37.
CRISPR-Cas9 gene drive control strategies use a homing selfish genetic element which induces a double-stranded break at the target site and is copied into the opposing chromosome, breaking an essential gene and ensuring super-Mendelian inheritance. During the copying process SNPs could potentially be transferred from one chromosome to another, converting tracts of the target to match the recipient. This would reduce the ability of gene drives to escape their genetic background of origin, with potential impacts on carrier fitness and the success of the strategy. In this study we use Anopheles gambiae strains with variation around the target site to determine the extent of chromosomal conversion during gene drive activity and the mechanism of inheritance bias. We confirm a homing-based mechanism and show that two thirds of homing events are resolved within 50 bp, showing that gene drive introgression into a wild strain can occur within one generation.
Repeat mediated excision of gene drive elements for restoring wild-type populations
28543Pratima R Chennuri, Josef Zapletal, Raquel D Monfardini, Martial Loth Ndeffo-Mbah, Zach N Adelman, Kevin M Myles, bioRxiv, 2023-11-28 11:32:14.
We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting the yellow gene of Drosophila melanogaster, replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts.
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.
Current Status of the Main Olive Pests: Useful Integrated Pest Management Strategies and Genetic Tools
28380E. Lantero, B. Matallanas and C. Callejas, Applied Sciences, 13. 2023-11-06 09:55:38.
Mediterranean olive cultivation faces challenges in the global environmental change context. Pests and diseases caused by arthropods such as Bactrocera oleae, Prays oleae, and certain vectors of Xylella fastidiosa are expected to increase and spread in part due to this global scenario. The control of these arthropods has relied on synthetic pesticides, the misuse of which has led to pest population resistance and concerns about their negative impacts on biodiversity and global health. Integrated pest management (IPM) methods have emerged through the careful consideration of all available control techniques and the subsequent integration of appropriate measures that discourage the development of pest populations. This paper reviews the IPM guidelines for olive cultivation, prioritizing the use of biological control methods, and the integration of genetics and biotechnology, which bring precision, efficacy, and safety. It evidences the importance of genetic analysis in pest populations, pesticide resistance and in the contributions of predators to pest control. Advances in formulations and delivery systems for pesticides such as Bacillus thuringiensis, plant-incorporated protectants, improved SIT techniques, and the specific efficacy of biologicals pesticides are covered. Finally, this paper explores promising tools such as RNAi and gene drive while recognizing the ethical, environmental, and regulatory challenges associated with their use. Shortly, these innovations have the potential to reduce the environmental impacts of pests while ensuring the long-term viability of the olive industry.
Mosquito gene targeted RNAi studies for vector control
25650M. Yadav, N. Dahiya and N. Sehrawat, Functional and Integrative Genomics, 23:180. 2023-05-25 07:55:21.
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
Synthetic gene drives as an anthropogenic evolutionary force
24895A. D. Cutter, Trends in Genetics, 2023-03-28 07:24:22.
Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of ‘genetic welding’ as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection. Genetic welding is capable of imposing complex and rapid heritable phenotypic change on entire populations, whether motivated by biodiversity conservation or public health. Unanticipated possible long-term evolutionary outcomes, however, demand further investigation and bioethical consideration. The emerging importance of genetic welding also compels our explicit recognition of genetic drive as an addition to the other four fundamental forces of evolution.
Gene Drive: Past, Present and Future Roads to Vertebrate Biocontrol
24780G. R. McFarlane, C. B. A. Whitelaw and S. G. Lillico, Applied Biosciences, 2:52-70. 2023-02-13 09:35:36.
Scientists have long sought a technology to humanely control populations of damaging invasive pests in a species-specific manner. Gene drive technology could see this become a reality. This review charts the twists and turns on the road to developing gene drives in vertebrates. We focus on rodents, as these will likely be the first targets, and trace the journey from the early understanding of selfish genetic elements to engineering gene drives in mice; before discussing future research focuses and the crucial role that public perception and governance will play in the application of this technology. The realisation of robust gene drive strategies in vertebrate pests has the potential to revolutionise biocontrol.
Meiotic transmission patterns of additional genomic elements in Brachionus asplanchnoidis, a rotifer with intraspecific genome size variation
24116J. Blommaert and C.-P. Stelzer, Scientific Reports, 12:20900. 2022-12-03 09:37:14.
Intraspecific genome size (GS) variation in Eukaryotes is often mediated by additional, nonessential genomic elements. Physically, such additional elements may be represented by supernumerary (B-)chromosomes or by large heterozygous insertions into the regular chromosome set. Here we analyze meiotic transmission patterns of Megabase-sized, independently segregating genomic elements (ISEs) in Brachionus asplanchnoidis, a planktonic rotifer that displays an up to two-fold intraspecific GS variation due to variation in size and number of these elements. To gain insights into the meiotic transmission patterns of ISEs, we measured GS distributions of haploid males produced by individual mother clones using flow cytometry and compared these distributions to theoretical distributions expected under a range of scenarios. These scenarios considered transmission biases resembling (meiotic) drive, or cosegregation biases, e.g., if pairs of ISEs preferentially migrated towards the same pole during meiosis. We found that the inferred transmission patterns were diverse and ranged from positive biases (suggesting drive) to negative biases (suggesting drag), depending on rotifer clone and its ISE composition. Additionally, we obtained evidence for a negative cosegregation bias in some of the rotifer clones, i.e., pairs of ISEs exhibited an increased probability of migrating towards opposite poles during meiosis. Strikingly, these transmission and segregation patterns were more similar among members of a genetically homogeneous inbred line than among outbred members of the population. Comparisons between early and late stages of haploid male embryonic development (e.g., young synchronized male eggs vs. hatched males) showed very similar GS distributions, suggesting that transmission biases occur very early in male development, or even during meiosis. Very large genome size was associated with reduced male embryonic survival, suggesting that excessive amounts of ISEs might be detrimental to male fitness. Altogether, our results indicate considerable functional diversity of ISEs in B. asplanchnoidis, with consequences on meiotic transmission and embryonic survival.
GMOs in Africa: Status, adoption and public acceptance
27490L. A. Gbadegesin, E. A. Ayeni, C. K. Tettey, V. A. Uyanga, O. O. Aluko, J. K. Ahiakpa, C. O. Okoye, J. I. Mbadianya, M. A. Adekoya, R. O. Aminu, F. P. Oyawole and P. Odufuwa, Food Control, 141:109193. 2022-11-01 13:46:04.
Globally, genetically modified (GM) crops contribute to food security by increasing crop yield, quality and shelf-life. The commercialisation and adoption of GM crops in many developed countries raised hope of improving food security and livelihood. Africa, a developing continent facing malnutrition, food crises and inadequate food production technologies has been slow to accept GM crops. The hesitancy to accept GM crops emanates from unfavourable policies shaped by public opinion, despite its potential for achieving the zero-hunger agenda. Impeding factors hampering the adoption of GM technology necessitate biosecurity regulations on GM crops to monitor the crop biosafety, environmental and health concerns. Herein, we reviewed GM crops status and adoption in Africa and possible constraints to their acceptance amidst some commercialised GM crops in African countries. Efforts aimed at improving GM adoption in Africa should include the provision of adequate monitoring and surveillance system, science-based policies, political will and a robust public education on GM technology.
Cross-kingdom RNAi to enhance the efficacy of insect pathogens
23851S. Asgari, Trends in Parasitology, 2022-10-25 10:11:07.
Insect pathogens play significant roles in the biocontrol of medical and agricultural pests. Cui et al. demonstrated that genetically modified (GM) fungi expressing host mosquito miRNAs could enhance the efficacy of the fungus by suppressing the host immune response. This opens avenues for utilisation of cross-kingdom RNAi in biocontrol.
Meiotic defects in human oocytes: Potential causes and clinical implications
23677T. Wu, H. Gu, Y. Luo, L. Wang and Q. Sang, BioEssays, 2022-10-07 08:30:48.
Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error-prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), and clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models.
Engineering RNA Interference-Based Dengue Virus Resistance in the Mosquito Vector Aedes aegypti: The Current Status and Future Directions
19969S. D. Denipitiyage, Y. I. N. S. Gunawardene, Z. Federico and R. S. Dassanayake, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:32:49.
Dengue is an acute, febrile disease caused by the dengue viruses (DENV) comprising four serotypes and transmitted by the mosquito vector Ae. aegypti. DENV are single-stranded, positive-sense RNA viruses of the family Flaviviridae. Dengue is declared as a current significant challenge in the Southeast Asia, imposing growing burden on infected populations. To date, dengue control has mostly relied on vector control strategies which have largely become ineffective. There is, therefore, an urgent need for novel vector control strategies. Development of genetically modified mosquito vectors to manipulate disease-vectoring populations has gathered increased interest in recent time. RNAi-mediated viral resistance contributes to the suppression of viruses, including DENV in the mosquito vector Ae. aegypti. With recent advances in the field of molecular biology, we and other scientists are continuing to engineer genes that confer virus resistance to reduce transmission rates of DENV and introducing these genes into the mosquito genome. Even though scientists successfully generated mosquito refractory to DENV2–4, no mosquito refractory to all four serotypes has been developed to date. This limitation can be overcome by systematic analysis of the molecular mechanisms of RNAi in the mosquito vector Ae. aegypti. An enhanced understanding of RNAi function in the mosquito vector Ae. aegypti will facilitate the application of RNAi to control the transmission of the dengue disease in the future. Here, based on current understanding of the RNAi, we discuss the mechanisms of RNAi in the mosquito vector Ae. aegypti. We also provide guidelines for optimal design of RNAi experiments in Ae. aegypti with the possible risks associated with them along with proposed solutions.
Empowering Indigenous Knowledge in Deliberations on Gene Editing in the Wild
19646R. Taitingfong and A. Ullah, Hastings Center Report, 51 Suppl 2:S74-s84. 2021-12-14 18:38:07.
Proposals to release genetically engineered organisms in the wild raise complex ethical issues related to their safe and equitable implementation. While there is broad agreement that community and public engagement is vital to decision-making in this context, more discussion is needed about who should be engaged in such activities and in what ways. This article identifies Indigenous peoples as key stakeholders in decisions about gene-editing in the wild and argues that engagement activities need not only include Indigenous peoples but also be designed, conducted, and analyzed in ways that confront longstanding power imbalances that dismiss Indigenous expertise. We offer specific recommendations to guide deliberative activities to not only be inclusive of Indigenous peoples but also to empower their diverse, situated knowledges. We call on those committed to the inclusive design of broad public deliberation to pursue strategies that shift dominant power dynamics to include Indigenous communities in more meaningful ways.
Gene drive and RNAi technologies: a bio-cultural review of next-generation tools for pest wasp management in New Zealand
19000S. Palmer, P. K. Dearden, O. R. Mercier, A. King-Hunt and P. J. Lester, Journal of the Royal Society of New Zealand, 1-18. 2021-10-14 15:09:43.
There is a global need for novel, next-generation technologies and techniques to manage pest species. We review work on potential step-changing technologies for large landscape (>1000 hectares) pest management of social Vespula wasps. We also review M?ori perspectives on these controls to gauge social and cultural acceptability to research, test and use of novel controls. Approaches discussed are the use of gene silencing (RNAi) and gene drives (CRISPR-Cas 9) involving genetic modification, which has potential for pest control but vary in feasibility, cost, benefits and off-target risks. RNAi may be better suited for wasp control in high-value cropping systems due to scaling inefficiencies. Gene drives offer potential for large-scale control but would require legislative and wide social deliberation due to their status as genetic modification. Both RNAi and gene drives will require consultation with tangata whenua. M?ori interest groups agreed that exotic wasps must be controlled and expressed aversion to non-targeted traditional control methods. We present a diversity of opinions in parallel with scientific research underscoring the need for continued dialogue with M?ori. Novel biotechnological controls must satisfy a broad range of social and cultural criteria, receive regulatory approval, along with being demonstrated as safe, selective, and cost-effective.
Persistent Spodoptera frugiperda rhabdovirus infection in Sf9 cells is not restricted by Wolbachia wMelPop-CLA and wAlbB strains and is targeted by the RNAi machinery
18362R. Parry, H. de Malmanche and S. Asgari, Virology, 563:82-87. 2021-09-08 14:28:58.
The endosymbiotic bacterium Wolbachia pipientis confers RNA virus refractoriness in Drosophila and Aedes mosquitoes. Questions remain about the Wolbachia-virus restriction phenotype and how extensive this phenomenon may be within other arthropods. Here, we generated two Spodoptera frugiperda cell lines stably transinfected with two strains of Wolbachia, wAlbB and wMelPop-CLA. Despite the high density of Wolbachia in stably infected Sf9 cells, RT-PCR indicated the presence of the negative-sense RNA virus Spodoptera frugiperda rhabdovirus (SfRV) in Wolbachia-infected and uninfected cell lines. No differences in the replication of SfRV between Sf9 and Wolbachia-infected cells was found. RNA-Seq analysis of the parental Sf9 cells supported SfRV's presence in these cells with abundant 20 nt virus-derived small RNAs indicating active replication of SfRV in these cells. Overall, this study supports a growing body of evidence that Wolbachia does not restrict negative-sense RNA viruses and generates an in vitro model to examine Lepidoptera-Wolbachia virus interactions.
New Pesticides Will Modify Insect Genes: What Could Go Wrong?
16587Food Tank, EcoWatch, 2021-03-09 19:44:05.
Farmers across the U.S. could soon fill their pesticide spray tanks with a substance known as interfering RNA (RNAi). (RNA is a molecule similar to DNA.) Insects that are exposed to it — either by eating crops sprayed with the substance or by landing on a crop and absorbing it through their bodies — would be genetically modified right there in the field. The pesticide would trigger a process inside the insects' cells to switch off or "silence" genes that are essential for survival — like those needed to make new, healthy cells — thus killing them.
RNAi-based products: A sustainable alternative to hazardous pesticides
16211Ghent University, Phys Org, 2021-01-27 13:59:48.
RNAi-based biocontrol is a great alternative to hazardous pesticides and can contribute towards reversing the alarming decline in farmland birds and beneficial insects (especially pollinating ones). RNAi is a well-known natural biological process in most
The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti
15482A. E. Williams, I. Sanchez-Vargas, W. R. Reid, J. Y. Lin, A. W. E. Franz and K. E. Olson, Viruses, 12:18. 2020-12-15 14:45:29.
We used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito's siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV.
Interdisciplinary development of a standardized introduction to gene drives for lay audiences
15381C. E. Schairer, C. Triplett, A. Buchman, O. S. Akbari and C. S. Bloss, BMC Medical Research Methodology, 20:15. 2020-12-10 15:09:37.
While there is wide consensus that the public should be consulted about emerging technology early in development, it is difficult to elicit public opinion about innovations unfamiliar to lay audiences. We sought public input on a program of research on genetic engineering to control mosquito vectors of disease that is led by scientists at the University of California and funded by the U.S. Defense Advanced Research Projects Agency (DARPA). In preparation for this effort, we developed a series of narrated slideshows to prompt responses to the development of gene drive mosquito control strategies among lay people. We describe the development and content of these slideshows and evaluate their ability to elicit discussions among focus group participants.
Suppressing evolution in genetically engineered systems through repeated supplementation
15188N. C. Layman, B. M. Tuschhoff, A. J. Basinski, C. H. Remien, J. J. Bull and S. L. Nuismer, Evolutionary Applications, 12. 2020-09-05 15:21:40.
Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms. One potential method to limit unwanted evolution is by taking advantage of the ability of gene flow to counter local adaption, a process of supplementation. Here, we investigate the feasibility of supplementation as a mechanism to offset the evolutionary degradation of a transgene in three model systems: a bioreactor, a gene drive, and a transmissible vaccine.
Mixed knobs in corn cobs
14581P. Lamelza and M. A. Lampson, Genes and Development, 34:1110-1112. 2020-08-20 14:31:38.
In this issue of Genes & Development, Swentowsky and colleagues (pp. 1239-1251) show that two types of knobs, those composed of 180-bp and TR1 sequences, recruit their own novel and divergent kinesin-14 family members to form neocentromeres.
Distinct kinesin motors drive two types of maize neocentromeres
14578K. W. Swentowsky, J. I. Gent, E. G. Lowry, V. Schubert, X. Ran, K. F. Tseng, A. E. Harkess, W. H. Qiu and R. K. Dawe, Genes and Development, 34:1239-1251. 2020-08-20 14:24:50.
Here we describe a second kinesin-14 gene, TR-1 kinesin (Trkin), that is required to mobilize neocentromeres made up of the minor tandem repeat TR-1.
Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers
13899M. A. Bravo Núñez, I. M. Sabbarini, L. E. Eide, R. L. Unckless and S. E. Zanders, eLife, 9:e57936. 2020-08-13 13:30:44.
Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.
Translating gene drive science to promote linguistic diversity in community and stakeholder engagement
12560C. Cheung, S. Gamez, R. Carballar-Lejarazú, V. Ferman, V. N. Vásquez, G. Terradas, J. Ishikawa, C. E. Schairer, E. Bier, J. M. Marshall, A. A. James, O. S. Akbari and C. S. Bloss, Global Public Health, 2020-06-26 18:55:10.
Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the technology in question may impact whole communities. We convened an interdisciplinary workgroup to translate previously developed narrated slideshows on gene drive mosquitoes from English into Spanish, reviewing each iteration for scientific accuracy and accessibility to laypeople. Using the finalised stimuli, we conducted five online, chat-based focus groups with Spanish-speaking adults from California. Overall, participants expressed interest in the topic and were able to summarise the information presented in their own words. Importantly, participants asked for clarification and expressed scepticism about the information presented, indicating critical engagement with the material. Through collaboration with Spanish-speaking scientists engaged in the development of GE methods of vector control, we translated highly technical scientific information into Spanish that successfully engaged Spanish-speaking participants in conversations about this topic. In this manuscript, we document the feasibility of consulting Spanish-speaking publics about a complex emerging technology by drawing on the linguistic diversity of the scientific teams developing the technology.
Can CRISPR gene drive work in pest and beneficial haplodiploid species?
12389J. Li, O. Aidlin Harari, A.-L. Doss, L. L. Walling, P. W. Atkinson, S. Morin and B. E. Tabashnik, Evolutionary Applications, 2020-06-03 18:14:33.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex-linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.
RNAi: Applications in Vertebrate Pest Management
14854K. E. Horak, Trends in Biotechnology, 38:1200-1202. 2020-05-25 17:42:08.
the development of novel control technologies must be focused on species specificity and low environmental impact. Sequence-specific gene silencing via RNAi holds promise for effective management of pest wildlife.
The Y Chromosome as a Battleground for Intragenomic Conflict
11962D. Bachtrog, Trends in Genetics, 2020-05-21 18:10:11.
Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.
Male-biased adult production of the striped fruit fly, Zeugodacus scutellata, by feeding dsRNA fpecific to Transformer-2
11271M. A. Al Baki, M. Vatanparast and Y. Kim, Insects, 11:211. 2020-03-28 19:17:02.
Sterile insect release technique (SIT) is effective for eradicating quarantine insects including various tephritid fruit flies. When SIT is used for fruit flies, it is challenging to remove females from sterile males due to oviposition-associated piercing damage. This study developed a sex transition technique by feeding double-stranded RNA (dsRNA) specific to a sex-determining gene, Transformer-2 (Zs-Tra2) of the striped fruit fly, Zeugodacus scutellata. Zs-Tra2 is homologous to other fruit fly orthologs. It is highly expressed in female adults. RNA interference (RNAi) of Zs-Tra2 by injecting or feeding its specific dsRNA to larvae significantly increased male ratio. Recombinant Escherichia coli cells expressing dsRNA specific to Zs-Tra2 were prepared and used to feed larvae to suppress Zs-Tra2 gene expression levels. When these recombinant bacteria were fed to larvae during the entire feeding stage, the test population was significantly male-biased. Some females treated with such recombinant E. coli exhibited mosaic morphological characters such as the presence of male-specific abdominal setae in females. This study proposes a novel technique by feeding dsRNA specific to Transformer-2 to reduce female production during mass-rearing of tephritid males for SIT.
Should the humans be allowed to genetically modify insects?
11222Olivia Abbe, NYK Daily, 2020-03-24 15:27:57.
Genetic engineering, also called Genetic modification or Genetic manipulation, is the direct manipulation of an organism’s genes using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA.
Gene Drive – The Concept Explained
11402GeneConvene Global Collaborative, 2020-03-20 12:59:44.
This short video is intended to serve as a short tutorial that explains the general idea of 'drive' or 'gene drive' in the context of genetics. It provides the viewer with a basic understanding of the key genetic processes underlying the patterns of inheritance with which most people of familiar and explains how these processes are involved in gene drive. This video focuses on genetics and not applications of gene drive technologies and associated issues.
Population-level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus
11212M. P. Edgington, T. Harvey-Samuel and L. Alphey, Evolutionary Applications, 10. 2020-03-06 14:52:40.
CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template-converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end-joining repair mechanisms produce cut-resistant alleles that rapidly induce drive failure. Multiplexing-simultaneously targeting multiple sites at the wild-type locus-is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut-resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population-level multiplexing approaches with standard individual-level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement, while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility, we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives
5626Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer, bioRxiv, 861435:861435. 2019-12-17 16:38:34.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based underdominance gene drive constructs employing toxin-antidote principles. These drives disrupt the wild-type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero invasion threshold frequency, referring to the critical frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same-site” and “distant-site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR toxin-antidote underdominance drive systems could allow for the design of highly flexible and potentially confinable gene drive strategies.
Genetic frontiers for conservation: An assessment of synthetic biology and biodiversity conservation
16089K. H. Redford, T. Brooks, M., B. W. Nicholas and J. S. A. Macfarlane, International Union for Conservation of Nature, 2019-12-01 15:41:26.
This assessment is the beginning of a process that will lead to the development of an IUCN policy to guide the Union’s Director General, Commissions, and Members. The draft policy will be discussed in many fora before it is brought to vote at the World Conservation Congress in 2020. Far greater public attention to the topic of synthetic biology and biodiversity conservation is essential, given the potential impact of scientific discoveries and policy decisions that may be just over the horizon, and also given the need for broad partnerships to address the challenges that the conservation and synthetic biology communities will inevitably face
Herbicide resistant weeds: A call to integrate conventional agricultural practices, molecular biology knowledge and new technologies
6040V. E. Perotti, A. S. Larran, V. E. Palmieri, A. K. Martinatto and H. R. Permingeat, Plant Science, 290:110255. 2019-09-06 21:01:14.
Herbicide resistant (HR) weeds are of major concern in modern agriculture. This situation is exacerbated by the massive adoption of herbicide-based technologies along with the overuse of a few active ingredients to control weeds over vast areas year after year. Also, many other anthropological, biological, and environmental factors have defined a higher rate of herbicide resistance evolution in numerous weed species around the world. This review focuses on two central points: 1) how these factors have affected the resistance evolution process; and 2) which cultural practices and new approaches would help to achieve an effective integrated weed management. We claim that global climate change is an unnoticed factor that may be acting on the selection of HR weeds, especially those evolving into non-target-site resistance mechanisms. And we present several new tools –such as Gene Drive and RNAi technologies- that may be adopted to cope with herbicide resistance spread, as well as discuss their potential application at field level. This is the first review that integrates agronomic and molecular knowledge of herbicide resistance. It covers not only the genetic basis of the most relevant resistance mechanisms but also the strengths and weaknesses of traditional and forthcoming agricultural practices.
What is genome editing?
14784NHGRI, NHGRI, 2019-08-15 17:41:15.
Genome editing is a method that lets scientists change the DNA of many organisms, including plants, bacteria, and animals. Editing DNA can lead to changes in physical traits, like eye color, and disease risk. Scientists use different technologies to do this.
The association between mitochondrial genetic variation and reduced colony fitness in an invasive wasp
13731J. Dobelmann, A. Alexander, J. W. Baty, N. J. Gemmell, M. A. M. Gruber, O. Quinn, T. Wenseleers and P. J. Lester, Molecular Ecology, 28:3324-3338. 2019-06-24 19:25:29.
Despite the mitochondrion's long-recognized role in energy production, mitochondrial DNA (mtDNA) variation commonly found in natural populations was assumed to be effectively neutral. However, variation in mtDNA has now been increasingly linked to phenotypic variation in life history traits and fitness. We examined whether the relative fitness in native and invasive common wasp (Vespula vulgaris) populations in Belgium and New Zealand (NZ), respectively, can be linked to mtDNA variation.
Meiotic drive shapes rates of karyotype evolution in mammals
5921Blackmon, H., J. Justison, I. Mayrose and E. E. Goldberg, Evolution, 73:511-523. 2019-03-01 16:47:19.
Chromosome number is perhaps the most basic characteristic of a genome, yet generalizations that can explain the evolution of this trait across large clades have remained elusive. Using karyotype data from over 1000 mammals, we developed and applied a phylogenetic model of chromosome evolution that links chromosome number changes with karyotype morphology. Using our model, we infer that rates of chromosome number evolution are significantly lower in species with karyotypes that consist of either all bibrachial or all monobrachial chromosomes than in species with a mix of both types of morphologies. We suggest that species with homogeneous karyotypes may represent cases where meiotic drive acts to stabilize the karyotype, favoring the chromosome morphologies already present in the genome. In contrast, rapid bouts of chromosome number evolution in taxa with mixed karyotypes may indicate that a switch in the polarity of female meiotic drive favors changes in chromosome number. We do not find any evidence that karyotype morphology affects rates of speciation or extinction. Furthermore, we document that switches in meiotic drive polarity are likely common and have occurred in most major clades of mammals, and that rapid remodeling of karyotypes may be more common than once thought.
CRISPR gene drive efficiency and resistance rate is highly heritable with no common genetic loci of large effect
3901Champer, JW, Z. X.; Luthra, A.; Reeves, R.; Chung, J.; Liu, C.; Lee, Y. L.; Liu, J. X.; Yang, E.; Messer, P. W.; Clark, A. G., Genetics, 212:333-341. 2019-01-19 00:00:00.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population over time. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would eventually halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation postfertilization in the early embryo ranged from 7 to 79% among lines and averaged 42 +/- 18%. We performed a genome-wide association study using our results in the DGRP lines, and found that the resistance and conversion rates were not explained by common alleles of large effect, but instead there were several genetic polymorphisms showing weak association. RNA interference knockdown of several genes containing these polymorphisms confirmed their effect, but the small effect sizes imply that their manipulation would likely yield only modest improvements to the efficacy of gene drives.
Spatial structure undermines parasite suppression by gene drive cargo
3896Bull, JJR, Christopher H.; Gomulkiewicz, Richard; Krone, Stephen M., PeerJ, 7:e7921. 2019-01-14 00:00:00.
Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.
Genetic villains: Killer meiotic drivers
3959Bravo Núñez, MAN, Nicole L.; Zanders, Sarah E., Trends in Genetics, 34:424-433. 2018-01-17 00:00:00.
Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.
Rapid comeback of males: evolution of male-killer suppression in a green lacewing population
3979Hayashi, MN, M.; Kageyama, D., Proceedings of the Royal Society B-Biological Sciences, 285:6. 2018-01-17 00:00:00.
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi. An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
THE NATIONAL BIOSAFETY TECHNICAL COMMISSION (CTNBio) NORMATIVE RESOLUTION No. 16, OF JANUARY 15, 2018
16083CTNBio, National Biosafety Technical Commission of Brasil, 2018-01-15 15:17:02.
Sets forth the technical requirements for submitting an inquiry to the CTNBio concerning Precision Breeding Innovation Techniques. THE NATIONAL BIOSAFETY TECHNICAL COMMISSION (CTNBio), using its legal and regulatory powers and in observance of sections XV and XVI of article 14 of Law No. 11.105 of March 24, 2005; Whereas there is a need to assess Precision Breeding Innovation (PBI) techniques, which also comprise the so-called New Breeding Technologies (NBTs) in the light of Law No. 11.105 of March 24, 2005;
Veni, vidi, vici: the success of wtf meiotic drivers in fission yeast
3990López Hernández, JFZ, Sarah E., Yeast, 35:447-453. 2018-01-08 00:00:00.
Meiotic drivers are selfish DNA loci that can bias their own transmission into gametes. Owing to their transmission advantages, meiotic drivers can spread in populations even if the drivers or linked variants decrease organismal fitness. Meiotic drive was first formally described in the 1950s and is thought to be a powerful force shaping eukaryotic genomes. Classic genetic analyses have detected the action of meiotic drivers in plants, filamentous fungi, insects and vertebrates. Several of these drive systems have limited experimental tractability and relatively little is known about the molecular mechanisms of meiotic drive. Recently, however, meiotic drivers were discovered in a yeast species. The Schizosaccharomyces pombe wtf gene family contains several active meiotic drive genes. This review summarizes what is known about the wtf family and highlights its potential as a highly tractable experimental model for molecular and evolutionary characterization of meiotic drive.
How selfish DNA hijacks its way into egg cells
13516Science, 2017-11-06 13:52:33.
This video was produced by Science magazine and explains and illustrates how gonotaxis or the asymmetrical allocation of chromosomes to developing female gametes occurs in mice. This video reflects an understanding of this process based on the publication by Akera et al (2017).
Genetic conflicts: the usual suspects and beyond
4058McLaughlin, RNM, H. S., Journal of Experimental Biology, 220:6-17. 2017-01-16 00:00:00.
Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements.
A bigger toolbox: Biotechnology in biodiversity conservation
6012R. T. Corlett, Trends in Biotechnology, 35:55-65. 2017-01-13 20:08:47.
Conservation biology needs a bigger toolbox to meet unprecedented challenges. Genomics, fueled by declining sequencing costs, offers novel tools with increased precision for genetic questions previously answered with a few molecular markers, as well as completely new possibilities. Metabarcoding promises quicker, cheaper, and more accurate assessments of biodiversity in groups that are difficult to assess by traditional methods, while sequencing low-quality DNA extends the range of useable materials to include museum specimens, archeological remains, and environmental samples. Genomic and transcriptomic data can be used to assess the potential of populations to adapt to new challenges. In the near future, gene-editing tools may help endangered species cope with change, while gene drives control unwanted species and help wanted ones. De-extinction has become a serious prospect.
Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies
4097Pugh, J, Journal of Medical Ethics, 42:578-581. 2016-01-15 00:00:00.
Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context.
Rapid evolution of yeast centromeres in the absence of drive
4233Bensasson, DZ, M.; Burt, A.; Koufopanou, V., Genetics, 178:2161-2167. 2008-01-11 00:00:00.
To find the most rapidly evolving regions in the yeast genome we compared most of chromosome III from three closely related lineages of the wild yeast Saccharomyces paradoxits. Unexpectedly, the centromere appears to be the fastest-evolving part of the chromosome, evolving even faster than DNA sequences unlikely to be under selective constraint (i.e., synonymous sites after correcting for codon usage bias and remnant transposable elements). Centromeres on other chromosomes also show an elevated rate of nucleotide substitution. Rapid centromere evolution has also been reported for some plants and animals and has been attributed to selection for inclusion in the egg or the ovule at female meiosis. But Saccharomyces yeasts have symmetrical meioses with all four products surviving, thus providing no opportunity for meiotic drive. In addition, yeast centromeres show the high levels of polymorphism expected tinder a neutral model of molecular evolution. We suggest that yeast centromeres suffer an elevated rate of mutation relative to other chromosomal regions and they change through a process of "centromere drift," not drive.
The distribution of B chromosomes across species
4297Palestis, BGT, R.; Burt, A.; Jones, R. N., Cytogenetic and Genome Research, 106:151-158. 2004-01-15 00:00:00.
In this review we look at the broad picture of how B chromosomes are distributed across a wide range of species. We review recent studies of the factors associated with the presence of Bs across species, and provide new analyses with updated data and additional variables. The major obstacle facing comparative studies of B chromosome distribution is variation among species in the intensity of cytogenetic study. Because Bs are, by definition, not present in all individuals of a species, they may often be overlooked in species that are rarely studied. We give examples of corrections for differences in study effort, and show that after a variety of such corrections, strong correlations remain. Several major biological factors are associated with the presence of B chromosomes. Among flowering plants, Bs are more likely to occur in outcrossing than in inbred species, and their presence is also positively correlated with genome size and negatively with chromosome number. They are no more frequent in polyploids than in diploids, nor in species with multiple ploidies. Among mammals, Bs are more likely to occur in species with karyotypes consisting of mostly acrocentric chromosomes. We find no evidence for an association with chromosome number or genome size in mammals, although the sample for genome size is small. The associations with breeding system and acrocentric chromosomes were both predicted in advance, but those with genome size and chromosome number were discovered empirically and we can offer only tentative explanations for the very strong associations we have uncovered. Our understanding of why B chromosomes are present in some species and absent in others is still in its infancy, and we suggest several potential avenues for future research. Copyright (C) 2004 S. Karger AG, Basel.
Homing endonuclease genes: the rise and fall and rise again of a selfish element
4286Burt, AK, V., Current Opinion in Genetics & Development, 14:609-615. 2004-01-04 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the opportunities for homing - in other words, the frequency with which HEG(+) and HEG(-) chromosomes come into contact - which varies widely among host taxa. HEGs are also unusual in that the selection pressure for endonuclease function disappears if they become fixed in a population, which makes them susceptible to degeneration and imposes a need for regular horizontal transmission between species. HEGs will be selected to reduce the harm done to the host organism, and this is expected to influence the evolution of their sequence specificity and maturase functions. HEGs may also be domesticated by their hosts, and are currently being put to human uses.
Site-specific selfish genes as tools for the control and genetic engineering of natural populations
4306Burt, A, Proceedings of the Royal Society B-Biological Sciences, 270:921-928. 2003-01-04 00:00:00.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.
Adaptation for horizontal transfer in a homing endonuclease
4323Koufopanou, VG, M. R.; Burt, A., Molecular Biology and Evolution, 19:239-246. 2002-01-21 00:00:00.
Selfish genes of no function other than self-propagation are susceptible to degeneration if they become fixed in a population. and regular transfer to new species may be the only means for their long-term persistence. To test this idea we surveyed 24 species of yeast for VDE, a nuclear. intein-associated homing endonuclease gene (HEG) originally discovered in Saccharomyces cerevisiae. Phylogenetic analyses show that horizontal transmission has been a regular occurrence in its evolutionary history. Moreover, VDE appears to be specifically adapted for horizontal transmission. Its 31-bp recognition sequence is an unusually well-conserved region in an unusually well-conserved gene. In addition, the nine nucleotide sites most critical for homing are also unusually well conserved. Such adaptation for horizontal transmission presumably arose as a consequence of selection, both among HEGs at different locations in the genome and among variant,,, at the same location. The frequency of horizontal transmission must therefore be a key feature constraining the distribution and abundance of these genes.
Outcrossed sex allows a selfish gene to invade yeast populations
4329Goddard, MRG, D.; Burt, A., Proceedings of the Royal Society B-Biological Sciences, 268:2537-2542. 2001-01-07 00:00:00.
Homing endonuclease genes (HEGs) in eukaryotes are optional genes that have no obvious effect on host phenotype except for causing chromosomes not containing a cop), of the gene to be cut, thus causing them to be inherited at a greater than Mendelian rate via gene conversion. These genes are therefore expected to increase in frequency in outcrossed populations, but not in obligately selfed populations. In order to test this idea, we compared the dynamics of the VDE HEG in six replicate outcrossed and inbred populations of yeast (Saccharomyces cerevisiae). VDE increased in frequency from 0.21 to 0.55 in four outcrossed generations, but showed no change in frequency in the inbred populations. The absence of change in the inbred populations indicates that any effect of VDE on mitotic replication rates is less than 1%. The data from the outcrossed populations best fit a model in which 82% of individuals are derived from outcrossing and VDE is inherited by 74% of the meiotic products from heterozygotes (as compared with 50% for Mendelian genes), These results empirically demonstrate how a host mating system plays a key role in determining the population dynamics of a selfish gene.
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