Keywords: Synthetic biology
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.
Three Stunning Ways Biologists Aim to Edit Animal and Plant Genes to Fight Diseases and Extinction
35386Sandy Ong, Smithsonian Magazine, 2026-01-21 16:42:41.
In the summer of 1904, Herman Merkel, chief forester at the Bronx Zoo, in New York City, was making his usual rounds across the property when he noticed something strange growing on American chestnut trees: misshapen constellations of swollen, orange-brown cankers. Unbeknownst to Merkel, his observations were the first signs of what would later be referred to as “the greatest ecological disaster in North America since the Ice Age.” Further investigation revealed that the culprit was a fungus called Cryphonectria parasitica, or chestnut blight, which slips its spores through cracks in the bark and fatally severs a tree’s water and nutrient supply. The pathogen was a stowaway that had arrived on imported Japanese chestnut trees, which are resistant—but on American soil, it proved to be a swift and merciless killer. Barely a year later, the blight had claimed nearly all the zoo’s chestnuts—as well as those in the surrounding Bronx parks. By the 1950s, it had wiped out 99 percent of the species’ population across the Eastern United States, where more than four billion of the towering trees had once so blanketed the landscape that a squirrel was said to be able to travel from Maine to Georgia on chestnut branches alone. Since then, scientists have tried, with little success, to bring the trees back from the brink. Today, American chestnuts are considered functionally extinct. Full-sized trees are hard to come by; mainly roots and shoots remain. Scientists have bred hybrid American-Chinese chestnut trees, but planting fully native species is important for ecological restoration goals, says Andrew Newhouse, director of the American Chestnut Research and Restoration Project at the State University of New York (SUNY). Thanks to an emerging field, the iconic trees—and other imperiled species—could one day be restored. The discipline, called synthetic biology, relies on editing organisms’ DNA to introduce new genes or modify existing ones, essentially reprogramming life to fight disease, clean up the environment, increase food production and more. For chestnut trees, making changes to their genome could boost their resistance to the blight.
Gene drives tested against real-world malaria diversity
35377Marchal, I, Nature Biotechnology, 44. 2026-01-16 16:30:43.
Gene drive technology, which uses genetic engineering to propagate selected genes throughout a population, is a potential strategy for blocking the spread of malaria, either by suppressing mosquito populations or by making them unable to transmit the disease. However, gene drive mosquitos have mainly been tested in laboratory settings with decade-old Plasmodium parasite strains, and it is unknown whether they can block the transmission of genetically diverse Plasmodium now in circulation. In an important step toward application, Habtewold et al. now report in Nature the adaptation of a previously developed gene drive strategy to an African context.
Synthetic biology approaches to generate temperature-sensitive alleles for the Sterile Insect Technique
35280Chun Yin Leung, Ernst A. Wimmer, Hassan M. M. Ahmed, Insect Science, 2025-11-03 11:22:09.
The Sterile Insect Technique (SIT) is an environmentally friendly, sustainable pest control approach, which uses large-scale releases of sterile insects to suppress or eradicate target populations through infertile matings. The efficiency of SIT is enhanced by male-only releases requiring genetic sexing strains (GSSs) that are classically based on selectable recessive visible markers or temperature-sensitive lethal (tsl) mutations and a rescue by a wild-type allele translocated to the male-determining chromosome. The transfer of identified or designed temperature-sensitive alleles might allow the generation of neoclassical GSSs in additional SIT target species. By using precise genome-editing tools, such as CRISPR/Cas, the creation of specific mutations in target genes and the integration of a wild-type copy is feasible without the introduction of foreign DNA. This might ease regulation of neoclassical GSSs, since they are not considered transgenic. However, integration and expression of genes at male-determining loci or chromosomes is not reliably established. Therefore, additional strategies to link temperature-sensitive phenotypes to female development are required, which could be achieved by targeting genes involved in dosage compensation or sex determination. To create temperature-sensitive alleles, rational protein design using advanced modeling and prediction tools to evaluate and tailor the effect of mutations on protein stability and temperature sensitivity can be used. In addition, emerging synthetic biology strategies such as temperature-inducible N-degrons or temperature-sensitive inteins provide powerful tools to generate temperature sensitivity. Such approaches should enable conditional control over proteins causing female lethality or sex conversion and therefore promise straightforward generic approaches to generate GSSs for male-only production in SIT target species.
The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae
35269Pei-Shi Yen, Sebald A N R Verkuijl, Paolo Capriotti, et al., G3 Genes|Genomes|Genetics, 2025-11-02 17:38:52.
The modification of mosquito populations at scale through CRISPR-Cas9-mediated homing gene drives is a promising route for malaria vector control. Integral gene drives (IGDs) are designed to utilise the regulatory sequences of endogenous genes to reduce the size of the modification required for nuclease and effector expression. In this study, we describe the creation and characterisation of the nanosd IGD, which targets and is inserted into the nanos gene of the malaria vector Anopheles gambiae, and show that it achieves high rates of gene drive (98.4% in females, 99.5% in males). We find that homozygous nanosd females but not males show impaired fecundity and exhibit variable degrees of ovary underdevelopment. Transcriptomic analysis of ovaries points to decreased transcript levels of the nanos gene when harbouring Cas9 and changes to other fertility-related genes. As a minimal genetic modification, nanosd does not induce widespread transcriptomic perturbations that would affect vector competence, and we show that its susceptibility to Plasmodium spp. and O’nyong nyong virus infection remains similar to wild-type mosquitoes. Importantly, we find that nanosd propagates efficiently in caged mosquito populations and is maintained as a source of Cas9 after the emergence of drive-resistant alleles, whilst also mobilising a non-autonomous antiparasitic effector modification. The nanosd gene drive shows promise as a genetic tool for malaria vector control via population modification, and we outline steps towards its further optimisation.
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.
Should genetically modified wildlife be banned? Scientists weigh the risks
35235Mariana Lenharo, Nature, 2025-10-10 16:01:10.
The global conservation community is debating whether to ban the release of genetically modified organisms into the wild. Dozens of non-governmental organizations have called for a moratorium on field applications of synthetic biology — a technology being studied as a tool to fight diseases, control pests and help endangered species — saying that the approach has unpredictable consequences. But some researchers argue that an outright ban is too restrictive, and could have negative consequences for human health and biodiversity. A proposal for a ban will face a vote next week at a congress of the International Union for Conservation of Nature (IUCN) in Abu Dhabi. The IUCN brings together governments and civil-society organizations to guide global conservation policy. Although decisions made by its members are not legally binding, they do influence legislation in many countries, says biologist Piero Genovesi, head of the Wildlife Service at the Italian Institute for Environmental Protection and Research in Rome. If members vote in favour of the proposed ban, it “could have stronger impacts in areas like Europe or Australia, where there are many lines of research focused on developing new tools based on synthetic biology for improving the efficacy of conservation action”, Genovesi says. He is among more than 240 scientists who have so far signed an open letter asking IUCN members to reject the moratorium.
Sequence mismatch between gene-drive and target-site flanking regions significantly impairs homing efficiency in Culex quinquefasciatus
35007Tim Harvey-Samuel, Rajdeep Kaur, Philip T Leftwich, et al., bioRxiv, 2025-08-04 11:03:26.
CRISPR/Cas9-based homing gene-drives (homing-drives) hold enormous potential as control tools for mosquito disease-vectors. These genomically-encoded technologies spread themselves through target populations by creating double-stranded DNA breaks on homologous chromosomes, into which the homing-drives are copied (homed). Homing is dependent on sequence homology between the genomic regions flanking the transgene insertion and the break site. Homing efficiency (i.e. copying rate) substantially impacts the power of these systems: less efficient homing-drives spread slower, have fewer applications and are more resistance-prone. Understanding what influences homing-drive efficiency is therefore vital to the successful use of these technologies. Here we report a novel mechanism by which a homing-drives efficiency can be significantly impaired by natural sequence variation within a population into which it is spreading. Using a kmo-targeting split homing-drive in the West Nile virus mosquito Culex quinquefasciatus, we found that target-site heterology (sequence mismatch between the genomic regions flanking the target cut-site and the homing-drive transgene) of less than 10% reduced homing efficiency by up to 54%. While substantial research effort has been dedicated to increasing homing-drive efficiency through optimisation of within-construct components, our results highlight that the real-world efficacy of these systems may in part depend on variation beyond these controllable factors.
Synthetically Assisted Conservation and the Application of Emerging Biological Technologies for the Protection of Biodiversity
34956Jedediah F. Brodie, Amanda Emmel, Blake Wiedenheft, et al., Conservation Letters, 8. 2025-07-08 13:20:29.
New tools of synthetic biology that enable precise manipulation of genomes, metabolic pathways, and ecosystems present new opportunities, risks, ethical dilemmas, and responsibilities for stewards of biodiversity. We argue that the risks and benefits of synthetic biology for use in biodiversity conservation, which we term “synthetically assisted conservation,” can be better understood, evaluated, and regulated by precisely defining the techniques in relation to well-established and regulated conservation frameworks: conservation translocation and integrated pest management. Synthetically assisted conservation translocation could include the release of genetically modified organisms for in situ conservation of genes or restoration of ecological functions, while a synthetically assisted application of integrated pest management could involve using genetic modifications propagated through gene drives to remove invasive species. Contextualizing the range of techniques as expansions of these frameworks clarifies how new approaches may impact conservation, facilitating risk assessment and responsible implementation. Decision-making may be informed by existing policy guidance in accordance with national and international regulations on conservation translocation and integrated pest management. Nevertheless, additional policy and evaluative guidelines are needed to keep pace with rapid technological growth and novel issues such as the release of genes (e.g., in pollen or marine-dispersed gametes) separate from live organisms.
The challenge of measuring mosquito flight performance: going beyond sterile insect technique and into transgenic and gene drive-based approaches
35311Paola Najera, Christian E. Ogaugwu, Tyler F. Chan, et al., Open Biology, 15. 2025-06-01 10:32:43.
Invasive insects inflict global costs of more than 70 billion USD annually by destroying crops and spreading disease-causing pathogens. Sterile insect technique (SIT), an insect population control method, involves the irradiation or chemical sterilization of insects to produce sterile males that are mass-released. SIT has proven effective in reducing populations of the Mediterranean fruit fly, Mexican fruit fly and screwworm fly. In the past decade, efforts to improve SIT with transgenic approaches have increased, including the development of potentially highly invasive gene drive transgenes. Determining flight capability is vital to the success of any insect control programme, and various flight assays can be used to analyse insect dispersal, flight behaviour and the mechanics behind flight. However, traditional flight assays such as mark–release–recapture become more challenging with transgenic or gene drive arthropods due to ecological concerns, while assays such as wind tunnels or flight mills/arenas may not capture the full range of flight abilities. This review seeks to cover current flight assays and their limitations as well as the requirements for flight assays to establish comparative flight ability for genetically modified insects to better prioritize strains prior to any potential field-based releases.
Global and regional updates on gene drive governance; AUDA-NEPAD update on regional work
34860African Genetic Biocontrol Consortium, YouTube, 2025-05-26 21:04:00.
AUDA-NEPAD update on regional work. Presentation on AUDA-NEPAD’s initiatives and progress in governance and capacity-building efforts related to synthetic biology, particularly on gene drives.
Overcoming drug-resistant tumors with selection gene drives
31594Hui Wang, Mingqi Xie, Cell Genomics, 4. 2024-09-17 12:48:55.
Drug resistance is a major hurdle prohibiting effective treatment of many diseases, including cancer. Using model-guided designs, Leighow et al.1 engineered a dual-switch selection gene drive system custom designed to combat drug-resistant tumors. By demonstrating remarkable killing efficacies in preclinical models using human non-small lung cancer cells in vitro and in mice, this work describes an attractive mindset to develop next-generation anticancer therapies.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
34760Chen, W., Guo, J., Liu, Y. et al., Nature Communications, 15. 2024-09-14 09:17:45.
CRISPR homing gene drives can suppress pest populations by targeting female fertility genes, converting wild-type alleles into drive alleles in the germline of drive heterozygotes. fsRIDL (female-specific Release of Insects carrying a Dominant Lethal) is a self-limiting population suppression strategy involving continual release of transgenic males carrying female lethal alleles. Here, we propose an improved pest suppression system called “Release of Insects carrying a Dominant-sterile Drive” (RIDD), combining performance characteristics of homing drive and fsRIDL. We construct a split RIDD system in Drosophila melanogaster by creating a 3-gRNA drive disrupting the doublesex female exon. Drive alleles bias their inheritance in males, while drive alleles and resistance alleles formed by end-joining cause dominant female sterility. Weekly releases of RIDD males progressively suppressed and eventually eliminated cage populations. Modeling shows that RIDD is substantially stronger than SIT and fsRIDL. RIDD is also self-limiting, potentially allowing targeted population suppression.
Programming tumor evolution with selection gene drives to proactively combat drug resistance
30886Leighow, S.M., Reynolds, J.A., Sokirniy, I. et al., Nature Biotechnology, 2024-07-07 21:29:46.
Most targeted anticancer therapies fail due to drug resistance evolution. Here we show that tumor evolution can be reproducibly redirected to engineer therapeutic opportunity, regardless of the exact ensemble of pre-existing genetic heterogeneity. We develop a selection gene drive system that is stably introduced into cancer cells and is composed of two genes, or switches, that couple an inducible fitness advantage with a shared fitness cost. Using stochastic models of evolutionary dynamics, we identify the design criteria for selection gene drives. We then build prototypes that harness the selective pressure of multiple approved tyrosine kinase inhibitors and employ therapeutic mechanisms as diverse as prodrug catalysis and immune activity induction. We show that selection gene drives can eradicate diverse forms of genetic resistance in vitro. Finally, we demonstrate that model-informed switch engagement effectively targets pre-existing resistance in mouse models of solid tumors. These results establish selection gene drives as a powerful framework for evolution-guided anticancer therapy.
First synthetic gene drive for plants could help eradicate weeds
30846Erik Stokstad, Science, 2024-06-28 11:39:25.
More than a decade ago, a research group used the genome editor CRISPR to put evolution on fast forward, spurring a gene to spread throughout a population of lab-reared fruit flies many times faster than it normally could in nature. Mosquitoes with CRISPR-based “gene drives” came soon after, then mice a few years later—advances that brought a fraught mix of technological promise and ethical complexity. Proponents tout gene drives as a way to prevent insect-borne diseases, wipe out rats and other invasive creatures, and even help prevent extinction of endangered species. But one set of organisms had stood apart from the excitement: plants. Now, geneticists report that synthetic gene drives can work in flora, too. Circumventing a long-standing hurdle, two teams have independently engineered Arabidopsis thaliana, a small mustard popular for lab work, to carry a genetic payload that is inherited by up to 99% of offspring. Modeling suggests a similar gene could permeate a natural plant population in 10 to 30 generations. “What they’ve achieved is pretty amazing,” says Paul Neve, a weed scientist at the University of Copenhagen. “It is clever and innovative.”
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
30350Ignacio Tolosana, Katie Willis, Austin Burt, Matthew Gribble, Tony Nolan, Andrea Crisanti, Federica Bernardini, bioRxiv, 2024-05-21 18:59:24.
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/or 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. Males are unaffected. To our knowledge, our system represents the first engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to 8 times more efficient for population suppression than optimal versions of other self-limiting strategies.
Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails
29102Michelle L. Johnson, Bruce A. Hay, Maciej Maselko, Nature Communications, 15. 2024-04-16 09:23:41.
Population-scale genome editing can be used to alter the composition or fate of wild populations. One approach to achieving these aims utilizes a synthetic gene drive element—a multi-gene cassette—to bring about an increase in the frequency of an existing allele. However, the use of gene drives is complicated by the multiple scientific, regulatory, and social issues associated with transgene persistence and gene flow. Alternatives in which transgenes are not driven could potentially avoid some of these issues. Here we propose an approach to population scale gene editing using a system we refer to as an Allele Sail. An Allele Sail consists of a genome editor (the Wind) that introduces DNA sequence edits (the Sail) at one or more sites, resulting in progeny that are viable and fertile. The editor, such as a sequence-specific nuclease, or a prime- or base-editor, is inherited in a Mendelian fashion. Meanwhile, the edits it creates experience an arithmetic, Super-Mendelian increase in frequency. We explore this system using agent-based modeling, and identify contexts in which a single, low frequency release of an editor brings edits to a very high frequency. We also identify conditions in which manipulation of sex determination can be used to bring about population suppression. Current regulatory frameworks often distinguish between transgenics as genetically modified organisms (GMOs), and their edited non-transgenic progeny as non-GMO. In this context an Allele Sail provides a path to alter traits and fates of wild populations in ways that may be considered more acceptable.
A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations
28857Anderson, M.A.E., Gonzalez, E., Edgington, M.P. et al., Nature Communications, 15. 2024-01-30 16:38:51.
Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.
A bumpy road ahead for genetic biocontainment
28833George, D.R., Danciu, M., Davenport, P.W. et al, Nature Communications, 2024-01-23 18:15:26.
The environmental release of bioengineered organisms is increasingly being suggested for a variety of applications, including bioremediation, biosequestration, bio-mining, environmental biosensing and conservation. The objectives of many environmental release applications shift the goals of biocontainment from preventing organism spread outside of closed spaces (e.g., laboratories or bioreactors) to managing the persistence of engineered organisms and their genetic material in open, dynamic environments. In the scientific literature, discussions of environmental release are often accompanied by calls for robust “intrinsic biocontainment”, where containment mechanisms are genetically engineered into the organism to limit and control its spread and persistence. A number of intrinsic biocontainment approaches have so far been proposed, and can be grouped into two overarching strategies. First, gene-flow barriers attempt to limit the spread of genetic material through lateral gene transfer, which refers to the ability of cells to directly exchange DNA molecules with one another or absorb DNA from external environmental sources. This can be accomplished through conditional lethality strategies (such as toxin anti-toxin systems or targeted DNA degradation), or through limiting plasmid replication or deleting natural competence genes from target cells. Second, strain/host control strategies seek to prevent survival and growth of engineered microbes outside specific environmental conditions using growth restriction and fitness control strategies such as metabolic auxotrophy, kill switches, and conditional essentiality. Over the past decade, researchers and developers have expanded the technical toolkit of intrinsic biocontainment techniques, with new approaches using orthogonal sequences, synthetic auxotrophy, CRISPR-based kill switches, sequence-entanglement, and “cell-free” systems.
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.
Programmed evolution: Using asexual gene drives to sculpt tumor populations and combat genetic diversity
28800Justin Pritchard, Scott Leighow, Joshua Reynolds et al., Research Square, 2024-01-15 17:07:16.
Resistance evolution is responsible for the failure of most targeted anticancer therapies. Tumor heterogeneity is so profound that pre-existing resistance is thought to be guaranteed at the time that advanced disease is detected. The practice of waiting for treatment failure and then responding to the refractory tumor with next-generation targeted therapies locks clinicians in an evolutionary arms race until no further treatment options are available. Here, we posit that disease evolution can be reproducibly reprogrammed to design more readily treated tumors, regardless of the exact ensemble of pre-existing genetic heterogeneity. To this end, we conceive of a modular genetic platform that couples an inducible fitness advantage with a shared fitness cost. Using stochastic models of evolutionary dynamics, we identify the design criteria of these “selection gene drives.” We then build prototypes that leverage the selective pressure of various approved tyrosine kinase inhibitors and employ therapeutic mechanisms as diverse as prodrug catalysis and immune activity induction. By using saturating mutagenesis across a drug target and genome-scale loss-of-function libraries, we show that our selection gene drives can eradicate extremely diverse forms of genetic resistance. Finally, using theory to guide treatment scheduling, we demonstrate that model-informed switch engagement can create dramatic in vivo efficacy. These results establish selection gene drives as a powerful new paradigm for evolution-guided anticancer therapy.
Population suppression with dominant female-lethal alleles is boosted by homing gene drive
28685Jinyu Zhu, Jingheng Chen, Yiran Liu, Xuejiao Xu, Jackson Champer, bioRxiv, 2023-12-07 10:24:25.
Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown to be an attractive alternative to older sterile insect technique based on radiation. Female-specific lethal alleles have substantially increased power, but still require large, sustained transgenic insect releases. Gene drive alleles bias their own inheritance to spread throughout populations, potentially allowing population suppression with a single, small-size release. However, suppression drives often suffer from efficiency issues, and the most well-studied type, homing drives, tend to spread without limit. In this study, we show that coupling female-specific lethal alleles with homing gene drive allowed substantial improvement in efficiency while still retaining the self-limiting nature (and thus confinement) of a lethal allele strategy. Using a mosquito model, we show the required releases sizes for population elimination in a variety of scenarios, including different density growth curves, with comparisons to other systems. Resistance alleles reduced the power of this method, but these could be overcome by targeting an essential gene with the drive while also providing rescue. A proof-of-principle demonstration of this system in Drosophila melanogaster was effective in both basing its inheritance and achieving high lethality among females that inherit the construct in the absence of antibiotic. Overall, our study shows that substantial improvements can be achieved in female-specific lethal systems for population suppression by combining them with a gene drive.
A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance
28651Jingheng Chen, Shibo Hou, Ruobing Feng, Xuejiao Xu, Nan Liang, Jackson Champer, bioRxiv, 2023-12-05 10:59:48.
CRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading desired genes throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we created a homing drive targeting the essential but haplosufficient hairy gene. Our strategy involves spreading the drive construct through the homing process, eliminating nonfunctional resistance, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version of hairy. This strategy eliminates resistance more slowly than a previous strategy targeting haplolethal genes, but it may be easier to construct in non-model organisms. Our drive inheritance rate was moderate, and multigenerational cage studies showed quick drive spread to 96-97% of the population. However, the drive failed to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs, a strategy that previously was successful at preventing functional resistance. Sequencing showed that these alleles had a large deletion and must have utilized an alternate start codon. The resistance allele had a modest fitness advantage over the drive in a cage study, which could prevent long-term persistence of the drive, especially if cargo genes had an additional fitness cost. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs.
Advances and challenges in synthetic biology for mosquito control
28545Shih-Che Weng, Reem A. Masri, Omar S. Akbari, Trends in Parasitology, 2023-11-28 11:40:23.
Mosquito-borne illnesses represent a significant global health peril, resulting in approximately one million fatalities annually. West Nile, dengue, Zika, and malaria are continuously expanding their global reach, driven by factors that escalate mosquito populations and pathogen transmission. Innovative control measures are imperative to combat these catastrophic ailments. Conventional approaches, such as eliminating breeding sites and using insecticides, have been helpful, but they face challenges such as insecticide resistance and environmental harm. Given the mounting severity of mosquito-borne diseases, there is promise in exploring innovative approaches using synthetic biology to bolster mosquitoes' resistance to pathogens, or even eliminate the mosquito vectors, as a means of control. This review outlines current strategies, future goals, and the importance of gene editing for global health defenses against mosquito-borne diseases.
Gene drives for the extinction of wild metapopulations
28504Jason W. Olejarz, Martin A. Nowak, Journal of Theoretical Biology, 2023-11-27 10:57:31.
Population-suppressing gene drives may be capable of extinguishing wild populations, with proposed applications in conservation, agriculture, and public health. However, unintended and potentially disastrous consequences of release of drive-engineered individuals are extremely difficult to predict. We propose a model for the dynamics of a sex ratio-biasing drive, and using simulations, we show that failure of the suppression drive is often a natural outcome due to stochastic and spatial effects. We further demonstrate rock–paper–scissors dynamics among wild-type, drive-infected, and extinct populations that can persist for arbitrarily long times. Gene drive-mediated extinction of wild populations entails critical complications that lurk far beyond the reach of laboratory-based studies. Our findings help in addressing these challenges.
A synthetic biology approach to transgene expression
27699P. Leftwich, T. , J. Purcell, C. , M. Anderson, A. E. , R. Fragkoudis, S. Basu, G. Lycett, T. and L. Alphey, bioRxiv, 2023.08.31.555539. 2023-08-31 09:13:32.
The ability to control gene expression is pivotal in genetic engineering and synthetic biology. However, in most non-model and pest insect species, empirical evidence for predictable modulation of gene expression levels is lacking. This knowledge gap is critical for genetic control systems, particularly in mosquitoes, where transgenic methods offer novel routes for pest control. Commonly, the choice of RNA polymerase II promoter (Pol II) is the primary method for controlling gene expression, but the options are limited. To address this, we developed a systematic approach to characterize modifications in translation initiation sequences (TIS) and 3' untranslated regions (UTR) of transgenes, enabling the creation of a toolbox for gene expression modulation in mosquitoes and potentially other insects. The approach demonstrated highly predictable gene expression changes across various cell lines and promoter sequences, representing a significant advancement in mosquito synthetic biology gene expression.Competing Interest StatementThe authors have declared no competing interest.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
26903C. Weizhe, G. Jialiang, L. Yiran and C. Jackson, bioRxiv, 2023.07.17.549342. 2023-07-17 11:00:13.
Gene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon in doublesex in Anopheles mosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that in Drosophila melanogaster, a 3-gRNA drive disrupting the doublesex female exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called Release of Insects carrying a Dominant-sterile Drive (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targeting dsx reached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.Competing Interest StatementThe authors have declared no competing interest.
Fighting the battle against evolution: designing genetically modified organisms for evolutionary stability
28008M. Arbel-Groissman, I. Menuhin-Gruman, D. Naki, S. Bergman and T. Tuller, Trends in Biotechnology, 2023-07-12 06:48:15.
Synthetic biology has made significant progress in many areas, but a major challenge that has received limited attention is the evolutionary stability of synthetic constructs made of heterologous genes. The expression of these constructs in microorganisms, that is, production of proteins that are not necessary for the organism, is a metabolic burden, leading to a decrease in relative fitness and make the synthetic constructs unstable over time. This is a significant concern for the synthetic biology community, particularly when it comes to bringing this technology out of the laboratory. In this review, we discuss the issue of evolutionary stability in synthetic biology and review the available tools to address this challenge
Steering and controlling evolution — from bioengineering to fighting pathogens
26463M. Lässig, V. Mustonen and A. Nourmohammad, Nature Reviews Genetics, 2023-07-03 07:31:07.
Control interventions steer the evolution of molecules, viruses, microorganisms or other cells towards a desired outcome. Applications range from engineering biomolecules and synthetic organisms to drug, therapy and vaccine design against pathogens and cancer. In all these instances, a control system alters the eco-evolutionary trajectory of a target system, inducing new functions or suppressing escape evolution. Here, we synthesize the objectives, mechanisms and dynamics of eco-evolutionary control in different biological systems. We discuss how the control system learns and processes information about the target system by sensing or measuring, through adaptive evolution or computational prediction of future trajectories. This information flow distinguishes pre-emptive control strategies by humans from feedback control in biotic systems. We establish a cost–benefit calculus to gauge and optimize control protocols, highlighting the fundamental link between predictability of evolution and efficacy of pre-emptive control.
Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages
25086A. Simoni, R. D'Amato, C. Taxiarchi, M. Galardini, A. Trusso, R. Minuz, S. Gilli, A. Somerville, D. Shittu, A. Khalil, R. Galizi and R. Muller, Research Square, 2023-04-24 06:46:30.
CRISPR-based gene drives have the potential to spread within a population and are considered as promising vector control tools. A doublesex-targeting gene drive was shown effective to suppress laboratory populations in both small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework demand for systems able to modulate or revert the action of gene drives, as part of post-release risk-mitigation plans. We developed an improved AcrIIA4-based anti-drive strain and showed inhibition of gene drive spread, in complex feeding and reproductive behavioural conditions. A stochastic model predicted the experimentally-observed genotypes dynamics in overlapping generations in medium- and large-sized cages and further demonstrated the effectiveness of anti-drive in different release and fitness scenarios. This study provides a further validation for the use of anti-drive system in controlling the spread of gene drive in Anopheles under complex behavioural conditions.
Engineering stringent genetic biocontainment of yeast with a protein stability switch
24034S. A. Hoffmann and Y. Cai, bioRxiv, 2022.11.24.517818. 2022-11-24 09:51:15.
Synthetic biology holds immense promise to tackle key problems we are facing, for instance in resource use, environmental health, and human health care. However, comprehensive safety measures are needed to deploy genetically engineered microorganisms in open-environment applications. Here, we describe a genetic biocontainment system based on conditional stability of essential proteins. We used a yeast-adapted destabilizing domain degron, which can be stabilized by estradiol addition (ERdd). Leveraging the yeast GFP collection and lab automation platforms, we ERdd-tagged 775 essential genes and screened for strains with estradiol dependent growth. Three genes, SPC110, DIS3 and RRP46, were found to be particularly suitable. Respective strains showed no growth defect in the presence of estradiol and strong growth inhibition in its absence. Of these, SPC110-ERdd offered the most stringent containment, with an escape frequency of 7.0x10-8, and full growth restoration at 100 nM estradiol. By systematically analysing the containment escapees, we identified the non- essential C-terminal region of SPC110 as target for escape mutations. Its removal decreased the escape frequency with a single ERdd tag further to 4.3x10-9. Combining SPC110-ERdd with a second ERdd tag on either DIS3 or RRP46 resulted in escape frequencies below the detection limit of the used assay (<2x10-10). Being based on conditional protein stability, this approach is mechanistically orthogonal to previously reported intrinsic biocontainment systems. It thus can be readily combined with other systems, for instance ones based on transcriptional or translational control of essential gene expression, to achieve multiplexed, extremely stringent control over the survival of engineered organisms.Competing Interest StatementThe authors have declared no competing interest.
Ethics of gene drive mosquitoes for malaria elimination
24071A. J. Roberts, McMaster University, 2022-10-24 10:34:04.
This thesis is concerned with presenting analyses regarding key ethical issues regarding and arising from the development and potential use of gene drive modified mosquitoes for the purpose of malaria elimination. Each of the chapters constituting this thesis offers a rigorously researched analysis which attempts to answer questions thus far unanswered in the academic literature. Chapter one explores whether the development and use of this technology can be fairly considered unethical in principle; concluding it cannot be. Chapter two explores the appropriate relationship between this technology and the precautionary principle, a prominent regulatory and governance principle which has been invoked as ostensible support for an indefinite global moratorium on all gene drive technology. The chapter concludes that the precautionary principle, at least as articulated by UNESCO, does not provide justification for a global moratorium on gene drive technology. In fact, the precautionary principle is likely unfit as a regulatory norm for some kinds of gene drive products and purposes. Chapter three was co-authored with Delphine Thizy, Global Stakeholder Engagement Manager for Target Malaria, one of the leading consortiums working on research and development of gene drive biotechnology for malaria control. Together we articulate the ethical principles selected to guide Target Malaria’s stakeholder engagement, as well as provide the rationale for their selection and expound upon some early lessons from their implementation. Chapter four offers an analysis with the goal of locating the ethically appropriate locus of political organization from which to seek permission for a gene drive modified organism release into the shared environment. The chapter considers the appropriateness of each of the following levels of political organization: consent of individuals, local communities, nation states, and international governance institutions. The conclusion arrived at, with some caveats, is that such a decision is most appropriately issued by a nation state.
Hurdles in responsive community engagement for the development of environmental biotechnologies
25089A. M. Normandin, L. M. Fitzgerald, J. Yip and S. W. Evans, Synthetic Biology, 7:ysac022. 2022-10-20 06:56:55.
Recent calls for engaging communities in biotechnology development do not draw enough attention to the hurdles that must be overcome for engagement strategies to effectively feed back into research design and conduct. These hurdles call into question many standard ways of operating and assessing in traditional scientific disciplines. The first steps in addressing these hurdles can be the most difficult. In reflecting on our own experiences in the early-stage development of environmental biotechnologies, we provide a set of techniques to help scientists and their collaborators learn to become more responsive to the needs and attitudes of communities with which they are engaging.Graphical Abstract
Rational engineering of a synthetic insect-bacterial mutualism
23473Y. Su, H.-C. Lin, L. S. Teh, F. Chevance, I. James, C. Mayfield, K. G. Golic, J. A. Gagnon, O. Rog and C. Dale, Current Biology, 2022-08-29 07:21:11.
Summary Many insects maintain mutualistic associations with bacterial endosymbionts, but little is known about how they originate in nature. In this study, we describe the establishment and manipulation of a synthetic insect-bacterial symbiosis in a weevil host. Following egg injection, the nascent symbiont colonized many tissues, including prototypical somatic and germinal bacteriomes, yielding maternal transmission over many generations. We then engineered the nascent symbiont to overproduce the aromatic amino acids tyrosine and phenylalanine, which facilitate weevil cuticle strengthening and accelerated larval development, replicating the function of mutualistic symbionts that are widely distributed among weevils and other beetles in nature. Our work provides empirical support for the notion that mutualistic symbioses can be initiated in insects by the acquisition of environmental bacteria. It also shows that certain bacterial genera, including the Sodalis spp. used in our study, are predisposed to develop these associations due to their ability to maintain benign infections and undergo vertical transmission in diverse insect hosts, facilitating the partner-fidelity feedback that is critical for the evolution of obligate mutualism. These experimental advances provide a new platform for laboratory studies focusing on the molecular mechanisms and evolutionary processes underlying insect-bacterial symbiosis.
Biologists engineered insect-bacterial mutualism in ‘bucket list’ achievement
23475Annonymous, @THEU, 2022-08-23 07:28:20.
A new paper in Current Biology authored by Crystal Su and other collaborators in the School of Biological Sciences describes the development of a novel, synthetic insect-bacterial symbiosis that is sustained through many insect generations by transovarial bacterial transmission. The symbiotic bacteria express a red fluorescent protein that is visible through the insect cuticle, facilitating characterization of the mechanics of infection and transmission in insect tissues and cells. In addition, Su et. al.engineered the bacteria to modify their ability to synthesize aromatic amino acids, which are used by the insect host to fuel cuticle strengthening. Correspondingly, insects maintaining bacteria that overproduce these nutrients exhibited stronger cuticles, signifying mutualistic function. The establishment of this synthetic symbiosis will facilitate detailed molecular genetic analysis of symbiotic interactions and presents a foundation for the use of genetically modified symbionts in the engineering of insects that transmit diseases of medical and agricultural importance. The paper is titled “Rational engineering of a synthetic insect-bacterial mutualism.”
Bayesian network-based risk assessment of synthetic biology: Simulating CRISPR-Cas9 gene drive dynamics in invasive rodent management
22516E. A. Brown, S. R. Eikenbary and W. G. Landis, Risk Analysis, 2022-05-14 07:22:34.
Gene drive technology has been proposed to control invasive rodent populations as an alternative to rodenticides. However, this approach has not undergone risk assessment that meets criteria established by Gene Drives on the Horizon, a 2016 report by the National Academies of Sciences, Engineering, and Medicine. To conduct a risk assessment of gene drives, we employed the Bayesian network-relative risk model to calculate the risk of mouse eradication on Southeast Farallon Island using a CRISPR-Cas9 homing gene drive construct. We modified and implemented the R-based model "MGDrivE" to simulate and compare 60 management strategies for gene drive rodent management. These scenarios spanned four gene drive mouse release schemes, three gene drive homing rates, three levels of supplemental rodenticide dose, and two timings of rodenticide application relative to gene drive release. Simulation results showed that applying a supplemental rodenticide simultaneously with gene drive mouse deployment resulted in faster eradication of the island mouse population. Gene drive homing rate had the highest influence on the overall probability of successful eradication, as increased gene drive accuracy reduces the likelihood of mice developing resistance to the CRISPR-Cas9 homing mechanism.
GeneConvene Global Collaborative Webinar Series | Demystifying the Convention on Biological Diversity – Seven Videos
21940Hector Quemada and David O'Brochta, GeneConvene Global Collaborative, 2022-04-28 12:39:49.
The Convention on Biological Diversity (CBD) is an international agreement aimed at providing the legal framework for country cooperation to conserve biodiversity, while also enabling its sustainable use, and providing for fair and equitable sharing of the benefits derived from that use. It became effective in 1993 when the first 30 countries signed it, but now has 196 parties. Biotechnology figures prominently in this agreement, since one of its major goal is to "promote and advance priority access on a fair and equitable basis by Contracting Parties, especially developing countries, to the results and benefits arising from biotechnologies." The CBD provides the basis for regulations on biotechnologies, particularly genetically engineered organisms (including gene drive organisms). While the convention, and its subsidiary agreements, have a significant impact on the regulatory environment within which synthetic gene drive research takes place, the procedures and decision-making processes connected with the CBD are often not transparent to researchers and others who do not closely follow the proceedings.
Insect pest management in the age of synthetic biology
18682R. Mateos Fernández, M. Petek, I. Gerasymenko, M. Juteršek, Š. Baebler, K. Kallam, E. Moreno Giménez, J. Gondolf, A. Nordmann, K. Gruden, D. Orzaez and N. J. Patron, Plant Biotechnology Journal, 2021-08-20 13:09:26.
Arthropod crop pests are responsible for 20% of global annual crop losses, a figure predicted to increase in a changing climate where the ranges of numerous species are projected to expand. At the same time, many insect species are beneficial, acting as pollinators and predators of pest species. For thousands of years, humans have used increasingly sophisticated chemical formulations to control insect pests but, as the scale of agriculture expanded to meet the needs of the global population, concerns about the negative impacts of agricultural practices on biodiversity have grown. While biological solutions, such as biological control agents and pheromones, have previously had relatively minor roles in pest management, biotechnology has opened the door to numerous new approaches for controlling insect pests. In this review, we look at how advances in synthetic biology and biotechnology are providing new options for pest control. We discuss emerging technologies for engineering resistant crops and insect populations and examine advances in biomanufacturing that are enabling the production of new products for pest control.
The legal regulation of gene drive technologies
16914C. Elves, Univeristy of Oxford, 2021-05-01 13:32:03.
Gene drive technologies purport to provide a panacea and yet in doing so present unprecedented risks that threaten to change, potentially irreversibly, the way in which we live in the world. Gene drive technologies raise questions about what ends societies ought to seek for their citizens, how they are constituted and how those ends might be attained. Despite this, current discussions surrounding gene drive technologies and their regulation focus almost exclusively on the technical implications. Drawing on the work of sociologists and STS scholars, this thesis argues that lawyers ought to think critically about the ways in which they go about developing their understandings of new technologies as regulatory objects. Lawyers need to evaluate and scrutinize the knowledge claims with which they are presented, and work to identify those extending beyond the required technical expertise, if the regulatory frames they build are to bear fidelity to the realities of the technology. This thesis draws out the regulatory disconnection generated by the current regulation of gene drive technologies through the existing European Union GMO regime. It then goes on to describe the ways in which regulatory reconnection might be achieved by constructing broader frames through which we describe gene drive technologies as a regulatory object. In thinking about how lawyers might go about broadening the frames that they build, this thesis takes examples from Public Health Law scholarship and legislation. In response to both the normative and epistemic lacunae highlighted above, this thesis develops an account of why and how ethical enquiry ought to play a significant role in informing our descriptions of gene drive technologies as regulatory objects. Furthermore, this thesis argues that ethical enquiry is capable of articulating questions to which technical experts must provide answers if we are to develop fuller understandings of the technologies we regulate. In this way, ethical enquiry can help lawyers bridge both the normative and epistemic gaps that they are so often faced with in the regulation of emerging technologies.
Developing GDi-CRISPR System for Multi-copy Integration in Saccharomyces cerevisiae
16544Z.-X. Zhang, Y.-Z. Wang, Y.-S. Xu, X.-M. Sun and H. Huang, Applied Biochemistry and Biotechnology, 2021-03-03 16:12:03.
This study aims to develop a low-cost and easy-to-use multi-copy integration tool in S. cerevisiae. Firstly, twenty-one Cas proteins from different microorganisms were tested in S. cerevisiae to find the functional Cas proteins with optimal cleavage ability. Results showed that eight Cas proteins can complete gene editing. However, most of the transformants have low copy numbers, which may be caused by high cutting efficiency exceeding the repair rate. Therefore, the effect of donor translocation order was further investigated. Results showed that 4 copies were obtained by donor first translocation. Then, the gene drive delta site integration system by the CRISPR system (GDi-CRISPR) was developed by combining gene drive principle and CRISPR system. To be clear, the gRNA was put into donor fragments. Then, both of them were integrated into the genome, which can drive further cutting and repair due to increasing number of gRNA. Instead of high-throughput screening or resistance pressure, 6 copies were obtained in only 5–6 days using the GDi-CRISPR system. It is expected to further advance the development of S. cerevisiae multi-copy integration tools.
Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive
16657K. P. Oh, A. B. Shiels, L. Shiels, D. V. Blondel, K. J. Campbell, J. R. Saah, A. L. Lloyd, P. Q. Thomas, F. Gould, Z. Abdo, J. R. Godwin and A. J. Piaggio, Evolutionary Applications, 2021-02-22 17:41:41.
Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications.
Plain language summary: How do we have a public conversation about new technologies for conservation? The possibilities and pitfalls of scientific language
16409Annonymous, Relational Thinking, 2021-02-17 18:30:27.
Having caused a catastrophic decline of animal species, people now look to new technologies to reverse the damage. Gene drive is a potential tool that could increase the proportion of male offspring in rat populations and eventually reduce their overall numbers. Some suggest this tool could eliminate rats from islands, like New Zealand, where rats have a devastating impact on native species. While holding much potential, the New Zealand public has shown hesitation towards genetic tools. In our study, we investigated how four articles, each emphasizing a different aspect of gene drive (i.e., humaneness, pragmatism, decision making, and scientific innovation), impacted opinion towards gene drive alongside people’s emotional responses, biases, and perceived risks towards the tool.
Scientifically framed gene drive communication perceived as credible but riskier
16406E. A. MacDonald, E. D. Edwards, J. Balanovic and F. Medvecky, People and Nature, 2021-02-17 18:23:29.
Framing is a communication technique in which certain beliefs or values are emphasized that resonate with the target audience. Framing may increase how much people objectively think about new information and update their opinions; framing may mitigate emo
Projects to target a range of pest control solutions
16366K. McCormack, The Chronicle, 2021-02-10 20:19:28.
With the annual national cost of established vertebrate pest animals estimated to be around $800 million, and over $4 billion for weeds, it’s in Australia’s best interest to try and tackle these pesky problems at their root causes. 19 projects will be funded following a competitive grant process to research and advance breakthrough solutions to control some of Australia’s worst established pest animals and weeds, including fall armyworm and prickly acacia. Minister for Agriculture, Drought and Emergency Management, David Littleproud, said he was delighted with the high calibre and diversity of projects coming from the popular grant round.
Assisting Evolution: How Far Should We Go to Help Species Adapt?
16369E. Kolbert, YaleEnvironment360, 2021-02-09 20:28:55.
It was a hot, intensely blue day in the Australian Outback, about 350 miles north of Adelaide. I was tagging along with Moseby as she checked the batteries on the motion-sensitive cameras that dot Arid Recovery, an ecosystem restoration project she and her husband launched in 1997. The project sprawls over 47 square miles of red earth and scrub. It’s entirely surrounded by a six-foot-tall fence, which is designed to keep out feral cats and foxes. Inside the main fence is a series of smaller fenced-in paddocks. Several years ago, Moseby decided to start adding cats into some of these. Her reasoning was simple and, in its own way, radical. The outback ecosystem had been so fundamentally changed, that, if the native animals were to survive, they would have to change, too. Perhaps they could be trained to avoid cats, which were introduced to the country by the British colonists and now can be found virtually everywhere in Australia, including most islands.
Should we dim the sun? Will we even have a choice
16384E. Klein, New York Times, 2021-02-09 15:06:18.
“Under a White Sky” is going to be on my best books of 2021 list. It’s a wonderful work. Kolbert is the Pulitzer Prize-winning author of “The Sixth Extinction,” which you may have read. She is a staff writer at The New Yorker and just one of the great science journalists of this time, and particularly one of the great climate journalists of this age. But this book, this book’s existence is evidence of how badly that fight is going. This is a book about what we are going to need to contemplate in the coming years that we don’t want to. It’s a book about taking responsibility for how irreversibly we have altered the natural world; how often we have tried to control it, and then watched those attempts at control fail; how often the best most scientific minds of the age have come up with some brilliant solution, implemented it, and then watched calamity result. And at the same time — and this is what makes the book so worthwhile — it is a book about how there is no going back. Not now, not ever. We are in the Anthropocene. The future from here is an endless layering on of new efforts to control the consequences of our past efforts. We don’t get to flinch or pretend we don’t have to contemplate any of this. We’ve gone too far. One of the hardest things to do as a writer — and I tell you this from personal experience — is to write ambivalence. It’s easy to write a polemic or a sharp take. It is hard to write down the middle path, where you are simply describing things as they are, knowing that every possible obvious answer you can come to is probably a bad one, knowing that the hubris embedded in past attempts to solve this problem means any future brilliant idea is likely to end that way, too, but that doesn’t mean we can do nothing. But Kolbert walks that path really beautifully here, which is why I wanted to talk to her for the show. As always, my email is [email protected]. I’m always interested to know who you’d like to see on the show. The weirder, the better. So send me your guest suggestions. Here’s Elizabeth Kolbert.
Public attitudes towards synthetic biology
16363CSIRO, Synthetic Biology Future Science Platform, 2021-02-08 20:06:39.
A national survey has been conducted by CSIRO’s Synthetic Biology Future Science Platform as an important first step in measuring public attitudes towards synthetic biology. The survey draws on the views of more than 8,000 Australians, and researchers are examining the data to determine current attitudes to these emerging technologies
In Our Image: The Ethics of CRISPR Genome Editing
16272J. C. Eissenberg, Biomolecular Concepts, 12:1-7. 2021-02-06 16:55:38.
Here, I discuss the ethics surrounding the transformative CRISPR/Cas9mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.
Playing God and tampering with nature: popular labels for real concerns in synthetic biology
16201L. Carter, A. Mankad, E. V. Hobman and N. B. Porter, Transgenic Research, 2021-01-27 15:26:41.
We present the findings from a large Australian study (N = 4593) which suggests ‘playing God’ objections and their variants can be multilayered and, at times, accompanied by meaningful information about risk perceptions. We use qualitative analysis of ope
The Promises and Realities of Integration in Synthetic Biology: A View From Social Science
16287L. Carter and A. Mankad, Frontiers in Bioengineering and Biotechnology, 8. 2021-01-21 17:25:32.
We take stock of thepromises and realities of science integration by sharing our experiences of embarking onthis very challenge in Australia. We conclude by offering suggestions for bringing aboutthe enabling conditions for improved integration across the natural and social sciences.Four key actions are articulated to help pivot synthetic biology toward a more integratedscientific endeavor: (a) formalizing inclusivity from inception to project conclusion; (b)valuing differing philosophical positions as a strength rather than a barrier; (c) acceptingthat integration takes persistence and communication but is immensely rewarding; and(d) promoting meaningful interactions, such as pursuing joint opportunities, co-designingand co-publishing research. We argue that these actions arekey enablers for realizingscience integration in synthetic biology.
Vector dynamics influence spatially imperfect genetic interventions against disease
16547M. K. Yuksel, C. H. Remien, B. Karki, J. J. Bull and S. M. Krone, Evolution, Medicine, and Public Health, 9:1-10. 2020-12-27 16:20:40.
In spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction. Here, we consider the sensitivity of this process to biological details: do simple generalities emerge that may facilitate interventions?We develop formal mathematical models of this process similar to standard Ross–Macdonald models, but (i) specifying spatial structure of two patches, with vector transmission blocked in one patch but not in the other, (ii) allowing temporary human movement (travel instead of migration) and (iii) considering two different modes of mosquito biting.We find that there is no invariant effect of disrupting spatial structure with travel.
New insect species made via genetic engineering
15610L. Leffer, SCIENCELINE, 2020-12-18 15:47:16.
A biotech fast-forward button for evolution is on the horizon. Researchers say they have used a novel genetic engineering method to create several new species of fruit fly in the lab for the first time — an achievement which might help put a future without malaria and other insect-borne diseases within reach. The approach, called synthetic speciation, could prove useful in creating safer pest-control technologies, says Maciej Maselko, a postdoctoral fellow studying synthetic biology at Macquarie University. In one far-off scenario, according to Maselko, synthetic speciation might even be applied to generate designer organisms that could pollinate plants or even detect landmines. Maselko and his team published their findings September 8 in Nature Communications. “Speciation has occurred billions of times on the planet, but hasn’t been engineerable [before],” says Michael Smanski, a molecular biologist at the University of Minnesota and member of the research team. Maselko, Smanski and their colleagues have previously used a similar method to engineer “species like” differences in yeast in 2018, but their more recent results are the first time the concept has been proven possible in a multicellular animal. This method could produce untold numbers of new animal varieties within months rather than millennia, Smanski says.
Governing New Biotechnologies for Biodiversity Conservation: Gene Drives, International Law, and Emerging Politics
14258J. L. Reynolds, Global Environmental Politics, 20:28-48. 2020-08-31 14:28:38.
This article describes and analyzes the international law and politics of gene drives’ research, development, and possible use, with an emphasis on their potential biodiversity applications.
Socrates Untenured: Ethics, Experts, and the Public in the Synthetic Age
13182C. Preston, ISSUES in Science and Technology, 2020-07-14 17:44:20.
C. Preston (2020). Three tools have transformed biotechnology over the past decade and a half. Gene reading has made it possible to quickly sequence the genome of any living creature. Gene synthesis has made it possible to construct DNA sequences in the lab from constituent chemicals. Gene editing has made it possible to place those sections into an existing DNA sequence at any point a technician chooses.
CRISPR/Cas9 gene drive technology to control transmission of vector-borne parasitic infections
12386M. Nateghi Rostami, Parasite Immunology, preprint:e12762. 2020-06-04 18:10:02.
Gene drive is the process of copying of an endonuclease-containing cassette that leads to increased frequency of inheritance of the desired traits in a targeted population. CRISPR/Cas9 technology is advancing genetic manipulation of insects in the field of gene drive experiments. The CRISPR/Cas9 drive could be engineered for genetic manipulation of parasites and/or vectors for disease control. A number of promising CRISPR/Cas9-based gene drive strategies that interfere with parasite development or impairs the reproductive capability of the insect vector, have been proposed in the laboratory for blocking transmission of malaria and leishmaniasis. Still several technical and ethical challenges remain to be addressed, none appear insuperable in this field.
Public Opinion Towards Gene Drive as a Pest Control Approach for Biodiversity Conservation and the Association of Underlying Worldviews
7348E. A. MacDonald, J. Balanovic, E. D. Edwards, W. Abrahamse, B. Frame, A. Greenaway, R. Kannemeyer, N. Kirk, F. Medvecky, T. L. Milfont, J. C. Russell and D. M. Tompkins, Environmental Communication-a Journal of Nature and Culture, 15:1-16. 2020-01-27 21:27:11.
Synthetic gene drive approaches are nascent technologies with potential applicability for pest control for conservation purposes. Responsible science mandates that society be engaged in a dialogue over new technology, particularly where there exist global ramifications as with gene drive. We hypothesize that public attitudes towards gene drive are not formed on scientific knowledge or demographics alone, but are heavily influenced by underlying worldviews, which encapsulate a broad and interactive system of attitudes, beliefs, and values. To test this, we conducted a national survey in New Zealand (n = 8199) and found that respondents clustered into four distinct segments with underlying worldviews, better able to explain attitudes toward gene drive than either the participants' scientific knowledge or other explanatory factors such demographics, political ideology or religiosity. We found that the use of gene drive for biodiversity conservation currently has moderate (32%) levels of support in New Zealand but that varied substantially across the four segments. Should gene drive become a technically viable approach for pest control, understanding the worldviews that shape public decision-making can guide a more empathetic engagement process and empower society to participate in informed decision-making about if and how gene drive should be used for conservation purposes.
Metaphor, Trust and Support for Non-native Species Control
13833P. A. Kohl, S. J. Collins and M. Eichholz, Environmental Communication, 14:672-685. 2020-01-07 15:29:47.
This experimental study used a representative sample of U.S. residents (N = 1,042) to test whether the use of the term "invasive" increases support for non-native species control efforts. The term invasive had a small influence on support for two out of three non-native species control methods. We also found stronger support for control methods using gene editing technologies than control methods using poison.
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
Gene Drives: Dynamics and Regulatory Matters-A Report from the Workshop “Evaluation of Spatial and Temporal Control of Gene Drives,” April 4-5, 2019, Vienna
12396B. Giese, J. L. Friess, N. H. Barton, P. W. Messer, F. Debarre, M. F. Schetelig, N. Windbichler, H. Meimberg and C. Boete, Bioessays, 41:3. 2019-10-07 18:26:19.
Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.
Synthetic Biology: Research Needs for Assessing Environmental Impacts
17467C. M. Warner, S. R. Carter, R. F. Lance, F. H. Crocker, H. N. Meeks, B. L. Adams, M. L. Magnuson, T. Rycroft, K. Pokrzywinski and E. J. Perkins, Synthetic Biology 2020: Frontiers in Risk Analysis and Governance, 2019-08-01 18:23:43.
Synthetic biology and its applications have the potential to greatly improve economic development, public health, environmental stewardship, technological advancement, and many other areas. In May 2017, sixty individuals gathered in Lexington, Massachusetts for a workshop sponsored by the U.S. Army Engineer Research and Development Center (ERDC) to discuss applications of synthetic biology with likely or intended interaction with the environment. Representatives from academia, government agencies, industry, and non-governmental organizations convened to identify knowledge gaps and research needs to assess potential environmental impacts from these technologies. The group discussed challenges in environmental risk assessment, regulation, and community engagement for emerging synthetic biology technologies. The workshop was structured around four hypothetical case studies, including the use of gene drive engineered organisms to control infectious disease vectors, engineered microbes for bioremediation, cell-free applications for advanced chemical production, and engineered viruses for water treatment. Meeting these research needs will facilitate appropriate environmental risk assessment and informed decision making for the development and potential deployment of synthetic biology organisms and components in the environment.
Synthetic Biology and the United Nations
7967H.-E. Lai, C. Canavan, L. Cameron, S. Moore, M. Danchenko, T. Kuiken, Z. Sekeyová and P. S. Freemont, Trends in Biotechnology, 37:1146-1151. 2019-06-27 14:42:54.
Synthetic biology is a rapidly emerging interdisciplinary field of science and engineering that aims to redesign living systems through reprogramming genetic information. The field has catalysed global debate among policymakers and publics. Here we describe how synthetic biology relates to these international deliberations, particularly the Convention on Biological Diversity (CBD).
Biological control of pests and a social model of animal welfare
16284A. Mankad, U. Kennedy and L. Carter, Journal of Environmental Management, 247:313-322. 2019-06-25 17:21:12.
We consider the role of perceived humaneness or, more accurately, animal welfare as it relates to managing invasive species from a scientific and social perspective. In order to highlight and articulate particular nuances and standards across different pest control contexts, we use three case examples (feral cats, wild rabbits, and invasive cane toads) and explore where biological pest control and animal welfare interests intersect.
The EU regulatory framework on genetically modified organisms (GMOs)
3893Bruetschy, C, Transgenic Research, 28:169-174. 2019-01-11 00:00:00.
The European Union (EU) legislation on genetically modified organisms (GMOs) aims to ensure a high level of protection for human, animal and environmental health and a well-functioning EU internal market. The framework regulates the release of GMOs into the environment and their use as, or in, food and feed. It has three main pillars: pre-market authorisation based on a prior risk assessment, traceability and labelling. Within this legal framework, the EU has authorised the placing on the market of 118 GMOs so far. These have been obtained through long-standing techniques of genetic modification, namely transgenesis. Following the adoption of the GMO legislation, new techniques of genetic modification, including new mutagenesis techniques, have been developed, which have raised questions regarding the applicability of the GMO legislation and attracted a lot of attention from stakeholders and the general public. This article provides an overview of EU GMO legislation and implementation of the EU Court of Justice ruling on organisms obtained by mutagenesis techniques, issued in July 2018. It also updates on the recent initiatives by the European Commission and EU Member States on new developments in biotechnology. The manuscript is based on the author's contribution at the OECD Conference on Genome Editing, Applications in Agriculture, Implications for Health, Environment and Regulation held in Paris on 28-29 June 2018. It is complemented with updated information.
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
What is CRISPR?
14778A. Vidyasagar, LiveScience, 2018-04-21 17:17:15.
CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns.
Gene Drives – Wundermittel? Biowaffe?
12380Swiss Academy of Sciences, 2018-02-19 21:02:40.
Gene drives are genetic elements that skew the pattern of inheritance of a given characteristic in sexually reproduc- ing organisms. They can be used to spread a characteristic that can alter or even reduce the numbers of individuals in wild populations of a certain species.
Report of the ad hoc technical expert group on synthetic biology
16073Ad Hoc Technical Working Group, Convention on Biological Diversity, 2017-12-08 14:12:31.
In decision XIII/17, the Conference of the Parties to the Convention on Biological Diversity commended the work of the online forum and the Ad Hoc Technical Expert Group on Synthetic Biology (AHTEG) and welcomed the conclusions and recommendations of the report of the AHTEG as a basis for further discussion. The Conference of the Parties also considered the operational definition useful as a starting point for the purpose of facilitating scientific and technical deliberations under the Convention and its Protocols and took note of the conclusion of the AHTEG that living organisms developed through synthetic biology are similar to living modified organisms (LMOs) as defined in the Cartagena Protocol. The Conference of the Parties noted that the general principles and methodologies for risk assessment under the Cartagena Protocol and existing biosafety frameworks provide a good basis for risk assessment of living organisms developed through synthetic biology, but such methodologies might need to be updated and adapted.
Genome editing: scientific opportunities, public interests and policy options in the European Union
16075EASAC, European Academies Science Advisory Council, 2017-03-01 14:41:21.
In many of the areas in which EASAC, the European Academies’ Science Advisory Council, works, where a large and solid body of knowledge is needed to inform the action of our societies, it is important to recognise that there is an intimate mix of science and values involved in discussion. Such discussions are most fruitful when both knowledge and values are well identified. This report presents a broad synthesis of genome editing, one of the newer aspects of the biosciences. It is our hope that presenting clearly the science involved – the duty of academies – will serve the ongoing discussions within society that the report recommends be vigorously pursued.
A transatlantic perspective on 20 emerging issues in biological engineering
4073Wintle, BCB, C. R.; Rhodes, C.; Molloy, J. C.; Millett, P.; Adam, L.; Breitling, R.; Carlson, R.; Casagrande, R.; Dando, M.; Doubleday, R.; Drexler, E.; Edwards, B.; Ellis, T.; Evans, N. G.; Hammond, R.; Haseloff, J.; Kahl, L.; Kuiken, T.; Lichman, B. R.; Matthewman, C. A.; Napier, J. A.; OhEigeartaigh, S. S.; Patron, N. J.; Perello, E.; Shapira, P.; Tait, J.; Takano, E.; Sutherland, W. J., eLife, 6:21. 2017-01-11 00:00:00.
Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.
Guidance on risk assessment of living modified organisms and monitoring in the context of risk assessment
16062Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management,, Convention on Biological Diversity, 2016-09-14 21:27:35.
This document was developed by the Ad Hoc Technical Expert Group (AHTEG) on Risk Assessment and Risk Management, with input from the Open-ended Online Expert Forum, in accordance with terms of reference set out by the Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol on Biosafety (COP-MOP) in its decisions BS-IV/11 and BSV/12 in response to an identified need for further guidance on risk assessment of LMOs. 4 It is intended to be a “living document” that may be updated and improved as appropriate and when mandated by the Parties to the Cartagena Protocol on Biosafety.
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Foundation for the
National Institutes of Health
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