Scholarly Literature
This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives). The latest are shown here.
Disclaimer>
A New Approach to Develop Resistant Cultivars Against the Plant Pathogens: CRISPR Drives
21915M. I. Tek and K. Budak, Frontiers in Plant Science, 13. 2022-04-27 08:43:50.
CRISPR drive is a recent and robust tool that allows durable genetic manipulation of the pest population like human disease vectors such as malaria vector mosquitos. In recent years, it has been suggested that CRISPR drives can also be used to control plant diseases, pests, and weeds. However, using a CRISPR drive in Arabidopsis for the first time in 2021 has been shown to use this technology in plant breeding to obtain homozygous parental lines. This perspective has proposed using CRISPR drive to develop pathogen-resistant cultivars by disrupting the susceptibility gene (S). In the breeding program, CRISPR is used to create S-gene mutations in two parental lines of hybrid cultivars. However, CRISPR must be reapplied or long-term backcrossed for the parental line to obtain homozygous S-mutant cultivars. When a parental line crosses with different parental lines to develop new hybrids, heterozygous S-mutations could not resist in hybrid against the pathogen. CRISPR drives are theoretically valid to develop homozygous S-mutant plants against pathogens by only routine pollination after CRISPR drive transformation to just one parental line. This way, breeders could use this parental line in different crossing combinations without reapplying the genome-editing technique or backcrossing. Moreover, CRISPR drive also could allow the development of marker-free resistant cultivars with modifications on the drive cassette.
Pilot trial using mass field-releases of sterile males produced with the incompatible and sterile insect techniques as part of integrated Aedes aegypti control in Mexico
22224A. Martín-Park, A. Che-Mendoza, Y. Contreras-Perera, S. Pérez-Carrillo, H. Puerta-Guardo, J. Villegas-Chim, G. Guillermo-May, A. Medina-Barreiro, H. Delfín-González, R. Méndez-Vales, S. Vázquez-Narvaez, J. Palacio-Vargas, F. Correa-Morales, G. Ayora-Tal, PLoS Negl Trop Dis, 16:e0010324. 2022-04-26 15:46:43.
We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0-75.2% suppression). CONCLUSIONS/SIGNIFICANCE: Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.
Recent advancements in CRISPR/Cas technology for accelerated crop improvement
21827D. Das, D. L. Singha, R. R. Paswan, N. Chowdhury, M. Sharma, P. S. Reddy and C. Chikkaputtaiah, Planta, 255:109. 2022-04-25 09:34:49.
The likelihood of reduced agricultural production due to highly turbulent climatic conditions increases as the global population expands. The second paradigm of stress-resilient crops with enhanced tolerance and increased productivity against various stresses is paramount to support global production and consumption equilibrium. Although traditional breeding approaches have substantially increased crop production and yield, effective strategies are anticipated to restore crop productivity even further in meeting the world’s increasing food demands. CRISPR/Cas, which originated in prokaryotes, has surfaced as a coveted genome editing tool in recent decades, reshaping plant molecular biology in unprecedented ways and paving the way for engineering stress-tolerant crops. CRISPR/Cas is distinguished by its efficiency, high target specificity, and modularity, enables precise genetic modification of crop plants, allowing for the creation of allelic variations in the germplasm and the development of novel and more productive agricultural practices. Additionally, a slew of advanced biotechnologies premised on the CRISPR/Cas methodologies have augmented fundamental research and plant synthetic biology toolkits. Here, we describe gene editing tools, including CRISPR/Cas and its imitative tools, such as base and prime editing, multiplex genome editing, chromosome engineering followed by their implications in crop genetic improvement. Further, we comprehensively discuss the latest developments of CRISPR/Cas technology including CRISPR-mediated gene drive, tissue-specific genome editing, dCas9 mediated epigenetic modification and programmed self-elimination of transgenes in plants. Finally, we highlight the applicability and scope of advanced CRISPR-based techniques in crop genetic improvement.
Biotechnological Road Map for Innovative Weed Management
22450A. C. S. Wong, K. Massel, Y. Lam, J. Hintzsche and B. S. Chauhan, Frontiers in Plant Science, 13. 2022-04-25 09:27:40.
In most agriculture farmlands, weed management is predominantly reliant on integrated weed management (IWM) strategies, such as herbicide application. However, the overuse and misuse of herbicides, coupled with the lack of novel active ingredients, has resulted in the uptrend of herbicide-resistant weeds globally. Moreover, weedy traits that contribute to weed seed bank persistence further exacerbate the challenges in weed management. Despite ongoing efforts in identifying and improving current weed management processes, the pressing need for novel control techniques in agricultural weed management should not be overlooked. The advent of CRISPR/Cas9 gene-editing systems, coupled with the recent advances in “omics” and cheaper sequencing technologies, has brought into focus the potential of managing weeds in farmlands through direct genetic control approaches, but could be achieved stably or transiently. These approaches encompass a range of technologies that could potentially manipulate expression of key genes in weeds to reduce its fitness and competitiveness, or, by altering the crop to improve its competitiveness or herbicide tolerance. The push for reducing or circumventing the use of chemicals in farmlands has provided an added incentive to develop practical and feasible molecular approaches for weed management, although there are significant technical, practical, and regulatory challenges for utilizing these prospective molecular technologies in weed management.
The evolutionary significance of meiotic drive
21913J. B. Searle and F. P.-M. de Villena, Heredity, 2022-04-25 08:34:39.
In this essay, we will focus on‘true meiotic drive’ where the distorted transmission does arise within meiosis itself (Zanders and Unckless2019),specifically in females. Here, the non-transmission of one of the products of meiotic division is inherent in the gametogenic process—with the formation of a polar body as the functionless by-product of division, with the egg continuing on as the viable entity. The meiotic drive is therefore the biased segregation in favour of one type of allele such that it is most commonly retained in the egg at the cost of the other type of allele, which most commonly ends up in the polar body. The biased segregation can occur at either the first or second division ofmeiosis—both of which generate a functionless polar body, suchthat there is ultimately only one viable product of the two divisions—the final version of the egg, which then becomes a zygote on fertilisation.
Role of CRISPR Technology in Gene Editing of Emerging and Re-emerging Vector Borne Disease
21811K. K. Mahto, P. Prasad, M. Kumar, H. Dubey and A. Ranjan, Recent Advances in Pathogen Interactions, Immunity, and Vector Control Strategies, 2022-04-23 05:49:18.
Vector borne diseases are rampant across the world. Due to spread and estab-lishment of vector species in different geographical areas, vector adaptation and resistance towards many insecticides the only option left is vector control for vari-ous vector borne diseases. Recent advancement in the field of genome editing have provided a variety of tools like, CRISPR, a novel genome editing techniques which can be applied for the control and prevention of many deadly diseases like dengue, chikungunya, filariasis, Japanese encephalitis and Zika. The present chapter is aimed to discuss the recent advancement in genome editing tools such as, their applica-tion, challenges, and limitations in vector control. Additionally, this chapter would potentially be advantageous to understand the hurdles, knowledge gaps in eliminating vector borne disease.
Wolbachia endosymbionts in two Anopheles species indicates independent acquisitions and lack of prophage elements
21788S. Quek, L. Cerdeira, C. L. Jeffries, S. Tomlinson, T. Walker, G. L. Hughes and E. Heinz, Microbial Genomics, 8. 2022-04-21 06:52:58.
Wolbachia is a genus of obligate bacterial endosymbionts that infect a diverse range of arthropod species as well as filarial nematodes, with its single described species, Wolbachia pipientis, divided into several ‘supergroups’ based on multilocus sequence typing. Wolbachia strains in mosquitoes have been shown to inhibit the transmission of human pathogens, including Plasmodium malaria parasites and arboviruses. Despite their large host range, Wolbachia strains within the major malaria vectors of the Anopheles gambiae and Anopheles funestus complexes appear at low density, established solely on PCR-based methods. Questions have been raised as to whether this represents a true endosymbiotic relationship. However, recent definitive evidence for two distinct, high-density strains of supergroup B Wolbachia within Anopheles demeilloni and Anopheles moucheti has opened exciting possibilities to explore naturally occurring Wolbachia endosymbionts in Anopheles for biocontrol strategies to block Plasmodium transmission. Here, we utilize genomic analyses to demonstrate that both Wolbachia strains have retained all key metabolic and transport pathways despite their smaller genome size, with this reduction potentially attributable to degenerated prophage regions. Even with this reduction, we confirmed the presence of cytoplasmic incompatibility (CI) factor genes within both strains, with wAnD maintaining intact copies of these genes while the cifB gene was interrupted in wAnM, so functional analysis is required to determine whether wAnM can induce CI. Additionally, phy logenetic analysis indicates that these Wolbachia strains may have been introduced into these two Anopheles species via horizontal transmission events, rather than by ancestral acquisition and subsequent loss events in the Anopheles gambiae species complex. These are the first Wolbachia genomes, to our knowledge, that enable us to study the relationship between natural strain Plasmodium malaria parasites and their anopheline hosts.
Aedes aegypti abundance and insecticide resistance profiles in the applying Wolbachia to eliminate dengue trial
21790W. Tantowijoyo, S. K. Tanamas, I. Nurhayati, S. Setyawan, N. Budiwati, I. Fitriana, I. Ernesia, D. S. Wardana, E. Supriyati, E. Arguni, Y. Meitika, E. Prabowo, B. Andari, B. R. Green, L. Hodgson, E. Rancès, P. A. Ryan, S. L. O'Neill, K. L. Anders, M. R. A, PLOS Neglected Tropical Diseases, 16:e0010284. 2022-04-20 07:01:27.
The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.
A metapopulation approach to identify targets for Wolbachia-based dengue control
22221A. Reyna-Lara, D. Soriano-Paños, J. H. Arias-Castro, H. J. Martínez and J. Gómez-Gardeñes, Chaos, 32:041105. 2022-04-18 15:42:29.
Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.
Environmental factors influence the local establishment of Wolbachia in Aedes aegypti mosquitoes in two small communities in central Vietnam [version 2]
21728N. T. Hien, D. D. Anh, N. H. Le, N. T. Yen, T. V. Phong, V. S. Nam, T. N. Duong, N. B. Nguyen, D. T. T. Huong, L. Q. Hung, C. N. T. Trinh, N. V. Hoang, V. Q. Mai, L. T. Nghia, N. T. Dong, L. H. Tho, S. Kutcher, T. P. Hurst, J. L. Montgomery, M. Woolfit, E, Gates Open Research, 5:147. 2022-04-18 09:54:42.
Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown to reduce transmission of dengue and other pathogens, under both laboratory and field conditions. Here we describe the entomological outcomes of wMel Wolbachia mosquito releases in two small communities in Nha Trang City in central Vietnam. Methods: The wMel strain of Wolbachia was backcrossed into local Aedes aegypti genotype and mosquito releases were undertaken by community members or by staff. Field monitoring was undertaken to track Wolbachia establishment in local Ae. aegypti mosquito populations. Ecological studies were undertaken to assess relationships between environmental factors and the spatial and temporal variability in Wolbachia infection prevalence in mosquitoes. Results: Releases of wMel Wolbachia Ae. aegypti mosquitoes in two small communities in Nha Trang City resulted in the initial establishment of Wolbachia in the local Ae. aegypti mosquitopopulations, followed by seasonal fluctuations in Wolbachia prevalence. There was significant small-scale spatial heterogeneity in Wolbachia infection prevalence in the Tri Nguyen Village site, resulting in the loss of wMel Wolbachia infection in mosquitoes in north and center areas, despite Wolbachia prevalence remaining high in mosquitoes in the south area. In the second site, Vinh Luong Ward, Wolbachia has persisted at a high level in mosquitoes throughout this site despite similar seasonal fluctuations in wMel Wolbachia prevalence. Conclusion: Seasonal variation in Wolbachia infection prevalence in mosquitoes was associated with elevated temperature conditions, and was possibly due to imperfect maternal transmission of Wolbachia. Heterogeneity in Wolbachia infection prevalence was found throughout one site, and indicates additional factors may influence Wolbachia establishment.
The sterile insect technique is protected from evolution of mate discrimination
21768J. J. Bull and R. Gomulkiewicz, PeerJ, 10:e13301. 2022-04-18 07:53:47.
Background The sterile insect technique (SIT) has been used to suppress and even extinguish pest insect populations. The method involves releasing artificially reared insects (usually males) that, when mating with wild individuals, sterilize the broods. If administered on a large enough scale, the sterility can collapse the population. Precedents from other forms of population suppression, especially chemicals, raise the possibility of resistance evolving against the SIT. Here, we consider resistance in the form of evolution of female discrimination to avoid mating with sterile males. Is resistance evolution expected? Methods We offer mathematical models to consider the dynamics of this process. Most of our models assume a constant-release protocol, in which the same density of males is released every generation, regardless of wild male density. A few models instead assume proportional release, in which sterile releases are adjusted to be a constant proportion of wild males. Results We generally find that the evolution of female discrimination, although favored by selection, will often be too slow to halt population collapse when a constant-release implementation of the SIT is applied appropriately and continually. The accelerating efficacy of sterile males in dominating matings as the population collapses works equally against discriminating females as against non-discriminating females, and rare genes for discrimination are too slow to ascend to prevent the loss of females that discriminate. Even when migration from source populations sustains the treated population, continued application of the SIT can prevent evolution of discrimination. However, periodic premature cessation of the SIT does allow discrimination to evolve. Likewise, use of a ‘proportional-release’ protocol is also prone to escape from extinction if discriminating genotypes exist in the population, even if those genotypes are initially rare. Overall, the SIT is robust against the evolution of mate discrimination provided care is taken to avoid some basic pitfalls. The models here provide insight for designing programs to avoid those pitfalls.
Propagation of seminal toxins through binary expression gene drives could suppress populations
21691J. Hurtado, S. Revale and L. M. Matzkin, Scientific Reports, 12:6332. 2022-04-15 08:22:57.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.
Mendelian nightmares: the germline-restricted chromosome of songbirds
21724P. Borodin, A. Chen, W. Forstmeier, S. Fouché, L. Malinovskaya, Y. Pei, R. Reifová, F. J. Ruiz-Ruano, S. A. Schlebusch, M. Sotelo-Muñoz, A. Torgasheva, N. Vontzou and A. Suh, Chromosome Res, 2022-04-13 09:33:56.
Germline-restricted chromosomes (GRCs) are accessory chromosomes that occur only in germ cells. They are eliminated from somatic cells through programmed DNA elimination during embryo development. GRCs have been observed in several unrelated animal taxa and show peculiar modes of non-Mendelian inheritance and within-individual elimination. Recent cytogenetic and phylogenomic evidence suggests that a GRC is present across the species-rich songbirds, but absent in non-passerine birds, implying that over half of all 10,500 bird species have extensive germline/soma genome differences. Here, we review recent insights gained from genomic, transcriptomic, and cytogenetic approaches with regard to the genetic content, phylogenetic distribution, and inheritance of the songbird GRC. While many questions remain unsolved in terms of GRC inheritance, elimination, and function, we discuss plausible scenarios and future directions for understanding this widespread form of programmed DNA elimination.
Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders
22219V. Jonsson, H. Awan, N. D. Jones, T. B. Johannesen, K. Thogersen, B. A. Steig, G. Andorsdottir and G. E. Tjonnfjord, Scientific Reports, 12:6138. 2022-04-12 15:37:58.
The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, <
The non-Mendelian behavior of plant B chromosomes
21722J. Chen, J. A. Birchler and A. Houben, Chromosome Res, 2022-04-12 09:30:19.
B chromosomes, also known as supernumerary chromosomes, are dispensable elements in the genome of many plants, animals, and fungi. Many B chromosomes have evolved one or more drive mechanisms to transmit themselves at a higher frequency than predicted by Mendelian genetics, and these mechanisms counteract the tendency of non-essential genetic elements to be lost over time. The frequency of Bs in a population results from a balance between their effect on host fitness and their transmission rate. Here, we will summarize the findings of the drive process of plant B chromosomes, focusing on maize and rye.
A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles
22572E. Yang, M. Metzloff, A. M. Langmuller, X. J. Xu, A. G. Clark, P. W. Messer and J. Champer, G3-Genes Genomes Genetics, 13. 2022-04-08 09:02:04.
Gene drives are engineered alleles that can bias inheritance in their favor, allowing them to spread throughout a population. They could potentially be used to modify or suppress pest populations, such as mosquitoes that spread diseases. CRISPR/Cas9 homing drives, which copy themselves by homology-directed repair in drive/wild-type heterozygotes, are a powerful form of gene drive, but they are vulnerable to resistance alleles that preserve the function of their target gene. Such resistance alleles can prevent successful population suppression. Here, we constructed a homing suppression drive in Drosophila melanogaster that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene. The selected gRNA target sites were close together, preventing reduction in drive conversion efficiency. The construct reached a moderate equilibrium frequency in cage populations without apparent formation of resistance alleles. However, a moderate fitness cost prevented elimination of the cage population, showing the importance of using highly efficient drives in a suppression strategy, even if resistance can be addressed. Nevertheless, our results experimentally demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
Cas9-mediated maternal-effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae
21663R. Carballar-Lejarazú, T. Tushar, T. B. Pham and A. A. James, Genetics, 2022-04-07 15:16:08.
CRISPR/Cas9 technologies are important tools for the development of gene-drive systems to modify mosquito vector populations to control the transmission of pathogens that cause diseases such as malaria. However, one of the challenges for current Cas9-based drive systems is their ability to produce drive-resistant alleles resulting from insertions and deletions (indels) caused principally by nonhomologous end-joining following chromosome cleavage. Rapid increases in the frequency of such alleles may impair gene-drive dynamics. We explored the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. We find that potential drive-resistant mutant alleles are generated largely during embryonic development, most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers.
A multi-disciplinary approach for a building common understanding of genetic engineering for malaria control in Burkina Faso
21637L. Pare Toe, N. Barry, A. D. Ky, S. Kekele, W. I. Meda, K. Bayala, et al., Humanities and Social Sciences Communications, 9. 2022-04-05 08:18:54.
Genetic engineering is a complex topic, even for scientists working in other areas, and even more so for those who lack a formal scientific training. To help gene specialists and affected communities talk with one another, international guidance documents have been published that promote dialogue and exchanges. The current paper explores collaboration among scientists of different disciplines as well as between scientists, the local communities, mediated by theatre actors to develop a conversation about Target Malaria’s work on genetic technologies to modify mosquitoes for malaria elimination in Burkina Faso. It focuses on the co-construction of meaning of key scientific concepts with a view to fostering productive collaboration between scientists and the local community. The community provided feedback on what was shared with them regarding the science being developed in the lab and in the field, which in turn informed aspects of the research itself, and the nature of the collaboration between the scientists and the local community.
Governing Gene Drive Technologies: A Qualitative Interview Study
23410N. de Graeff, K. R. Jongsma, J. E. Lunshof and A. L. Bredenoord, AJOB Empirical Bioethics, 13:107-124. 2022-04-04 12:10:12.
Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth.Methods A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically.Results Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment.Conclusions The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations.
Expanding the flexibility of genome editing approaches for population control of the malaria mosquito
22226N. Kranjc, Imperial College London-PhD, 2022-04-01 15:50:55.
Discovery and adaptation of CRISPR-Cas systems for genome editing have allowed us to gain an efficient and yet simple tool for genetic manipulation in various fields of molecular biology and biotechnology. One of the most promising applications is the use of CRISPR-Cas9 endonuclease for gene drive systems as a population control strategy for various insect pests of medical and agricultural importance. Use of CRISPR-Cas9 endonuclease in gene drive applications has shown great promise in the laboratory, particularly for the control of Anopheles gambiae, the major vector of malaria. However, the performance of such gene drives can be limited by the range of available target sequences and by a propensity of existing endonuclease formulations to generate resistant mutations that hinder the gene drive’s efficiency. To expand the flexibility of gene drive systems, computational analysis was performed to identify additional Cas9 orthologs and their specificities that could usefully augment the targeting range of endonuclease-based gene drives. Two alternative variants of CRISPR-Cas endonucleases found in the bacterial species Lactobacillus rhamnosus and Bacteroides fragilis were assessed for their potential to expand the targeting space in the genome Anopheles gambiae. In addition, a computational tool was developed that evaluates neighbouring sequences to the target site to measure both its likely functional constraint and its likely propensity for DNA repair that could generate in-frame alleles. Using this approach we were able to generate a prioritized list of Anopheles gambiae target sites for gene drive applications that are less likely to be compromised by resistant alleles.
Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org