Article
Multidisciplinary Sciences
Kathryn Rozen-Gagnon, Soon Yi, Eliana Jacobson, Sasha Novack, Charles M. Rice
Summary: This study developed a mosquito-optimized, plasmid-based CRISPR/Cas9 system for use in U4.4 (Ae. albopictus) and Aag2 (Ae. aegypti) cell lines, demonstrating highly efficient editing of the AGO1 locus. The experimentally verified plasmids are versatile, cost-effective, and efficiently edit immune competent mosquito cell lines commonly used in arbovirus studies, enabling knock-in of a 3xFLAG tag at the N-terminus of endogenous AGO1.
SCIENTIFIC REPORTS
(2021)
Article
Entomology
Tran Zen B. Torres, Brian C. Prince, Alexis Robison, Claudia Ruckert
Summary: Culex mosquitoes are important vectors of mosquito-borne diseases, but effective treatments and vaccines are still lacking. Investigating the antiviral genes of Culex mosquitoes and developing gene-based vector control strategies are crucial. In this study, a Culex-optimized CRISPR/Cas9 plasmid was developed and characterized, providing a valuable tool for studying gene functions in Culex mosquito cell lines.
Article
Multidisciplinary Sciences
Joanna K. Konopka, Darya Task, Danny Poinapen, Christopher J. Potter
Summary: This study labeled all neurons in the sensory appendages of Anopheles mosquitoes using a neurogenetic approach. They also characterized the neurons in the chemosensory appendages and predicted the expression of ionotropic receptors and other chemosensory receptors. The findings provide a valuable genetic tool for studying the neurobiology and behavior of Anopheles mosquitoes.
Article
Genetics & Heredity
Rebeca Carballar-Lejarazu, Taylor Tushar, Thai Binh Pham, Anthony A. James
Summary: CRISPR/Cas9 technologies are important for controlling the transmission of pathogens by modifying mosquito populations. However, a challenge in current drive systems is the generation of drive-resistant alleles. This study finds that potential drive-resistant mutant alleles are mostly generated during embryonic development, likely due to the deposition of Cas9 endonuclease and guide RNAs by gene-drive mothers.
Article
Multidisciplinary Sciences
Gerard Terradas, Anna B. Buchman, Jared B. Bennett, Isaiah Shriner, John M. Marshall, Omar S. Akbari, Ethan Bier
Summary: CRISPR-based gene-drive systems have the potential to revolutionize vector control, but mutant alleles resistant to Cas9 cleavage can interrupt gene spread. Targeting essential genes with recoded rescue elements may reduce the appearance of NHEJ alleles and leave no trace of Cas9.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Yuemeng Zhao, Fei Wang, Changhong Wang, Xiaobai Zhang, Cizhong Jiang, Feng Ding, Li Shen, Qingfeng Zhang
Summary: Researchers have developed an integrating strategy based on the CRISPR/Cas9 system to generate a Cas9i system, which significantly reduces the time for creating transgenic strains in P. falciparum. They have successfully achieved multiplexed genome editing (mutating or tagging) in P. falciparum with this Cas9i system through a single-round transfection. Additionally, they have adapted AsCpf1 as an alternative to Cas9 in P. falciparum parasites for gene editing, marking a significant step in optimizing the CRISPR/Cas system for malaria parasite research.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lin Ling, Alexander S. Raikhel
Summary: Female mosquitoes feed on carbohydrates and proteins during each gonadotrophic cycle to become reproductively competent, with metabolism synchronized to support this process. The hormones juvenile hormone and ecdysteroids play key roles in female mosquito reproduction, while insulin-like peptides are critical for controlling metabolism. The JH and 20E pathways regulate protein levels of ILPs, establishing a regulatory axis for metabolism during gonadotrophic cycles.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Lin Ling, Alexander S. Raikhel
Summary: This study revealed that the amino acid (AA)/target of rapamycin (TOR) signaling pathway regulates the insulin-like peptides (ILPs) through GATA transcription factors (TFs), thereby controlling the metabolic requirements of reproducing female mosquitoes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Multidisciplinary Sciences
Sam Jones
Summary: Gene-drive technology in mosquitoes is advancing, yet unanswered questions remain before its deployment as a malaria-fighting technique.
Review
Biochemistry & Molecular Biology
Si-Wei Wang, Chao Gao, Yi-Min Zheng, Li Yi, Jia-Cheng Lu, Xiao-Yong Huang, Jia-Bin Cai, Peng-Fei Zhang, Yue-Hong Cui, Ai-Wu Ke
Summary: The CRISPR/Cas9 gene editing technology has made significant progress in oncological research, providing a powerful tool for exploring the mechanism of cancer, establishing tumor models, and studying drug targets.
Article
Multidisciplinary Sciences
Andrew Hammond, Paola Pollegioni, Tania Persampieri, Ace North, Roxana Minuz, Alessandro Trusso, Alessandro Bucci, Kyros Kyrou, Ioanna Morianou, Alekos Simoni, Tony Nolan, Ruth Mueller, Andrea Crisanti
Summary: This study demonstrates the suppressive activity of a CRISPR-based gene-drive targeting the doublesex gene in Anopheles gambiae populations. The gene-drive element spreads rapidly through the populations, achieving full suppression within one year without inducing resistance. Approximate Bayesian computation allows for a more accurate prediction of gene-drive behavior in ecologically-relevant settings.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
J. Boutin, J. Rosier, D. Cappellen, F. Prat, J. Toutain, P. Pennamen, J. Bouron, C. Rooryck, J. P. Merlio, I. Lamrissi-Garcia, G. Cullot, S. Amintas, V. Guyonnet-Duperat, C. Ged, J. M. Blouin, E. Richard, S. Dabernat, F. Moreau-Gaudry, A. Bedel
Summary: The study reveals the genotoxicity caused by CRISPR-Cas9 leading to loss of heterozygosity changes, while also highlighting the potential safety concerns of this technology for gene therapy.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Chaya T. L. Yuen, Dawn G. L. Thean, Becky K. C. Chan, Peng Zhou, Cynthia C. S. Kwok, Hoi Yee Chu, Maggie S. H. Cheung, Bei Wang, Yee Man Chan, Silvia Y. L. Mak, Anskar Y. Leung, Gigi C. G. Choi, Zongli Zheng, Alan S. L. Wong
Summary: Researchers have enhanced editing accuracy and reduced off-target edits by re-engineering KKH-SaCas9 with a Y239H mutation and a set of additional mutations, demonstrating the feasibility of multi-domain combinatorial mutagenesis to optimize editing fidelity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Immunology
Johanna Hoshizaki, Hannah Jagoe, Marcus C. S. Lee
Summary: CRISPR editing enables efficient generation of fluorescently labeled parasite lines, facilitating a deeper understanding of parasite biology.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Seong-Kyun Lee, Tuyet Kha Nguyen, Franziska Mohring, Jin-Hee Han, Egy Rahman Firdaus, Sung-Hun Na, Won-Sun Park, Robert W. Moon, Eun-Taek Han
Summary: This study investigated the function of Plasmodium knowlesi merozoite surface protein 1 paralog (PkMSP1P) through recombinant protein and gene editing techniques. The results demonstrated that PkMSP1P is involved in the in vitro growth of P. knowlesi, playing a distinct role from PkMSP1. Additionally, the study revealed immune cross-reactivity between PkMSP1P-19 antibodies and PkMSP1-19.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Tin-Yu J. Hui, Austin Burt
Article
Biotechnology & Applied Microbiology
Alekos Simoni, Andrew M. Hammond, Andrea K. Beaghton, Roberto Galizi, Chrysanthi Taxiarchi, Kyros Kyrou, Dario Meacci, Matthew Gribble, Giulia Morselli, Austin Burt, Tony Nolan, Andrea Crisanti
NATURE BIOTECHNOLOGY
(2020)
Correction
Biotechnology & Applied Microbiology
Alekos Simoni, Andrew M. Hammond, Andrea K. Beaghton, Roberto Galizi, Chrysanthi Taxiarchi, Kyros Kyrou, Dario Meacci, Matthew Gribble, Giulia Morselli, Austin Burt, Tony Nolan, Andrea Crisanti
NATURE BIOTECHNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Chris S. Clarkson, Alistair Miles, Nicholas J. Harding, Eric R. Lucas, C. J. Battey, Jorge Edouardo Amaya-Romero, Andrew D. Kern, Michael C. Fontaine, Martin J. Donnelly, Mara K. N. Lawniczak, Dominic P. Kwiatkowski, Martin J. Donnelly, Diego Ayala, Nora J. Besansky, Austin Burt, Beniamino Caputo, Alessandra della Torre, Michael C. Fontaine, H. Charles J. Godfray, Matthew W. Hahn, Andrew D. Kern, Dominic P. Kwiatkowski, Mara K. N. Lawniczak, Janet Midega, Samantha O'Loughlin, Joao Pinto, Michelle M. Riehle, Igor Sharakhov, Daniel R. Schrider, Kenneth D. Vernick, David Weetman, Craig S. Wilding, Bradley J. White, Arlete D. Troco, Joao Pinto, Jorge Cano, Abdoulaye Diabate, Austin Burt, Carlo Costantini, Kyanne R. Rohatgi, Nora J. Besansky, Edi Constant, David Weetman, Nohal Elissa, Davis C. Nwakanma, Musa Jawara, John Essandoh, Boubacar Coulibaly, Michelle M. Riehle, Kenneth D. Vernick, Joao Dinis, Janet Midega, Charles Mbogo, Philip Bejon, Gilbert Le Goff, Vincent Robert, Craig S. Wilding, Henry D. Mawejje, Martin J. Donnelly, Jim Stalker, Kirk A. Rockett, Eleanor Drury, Daniel Mead, Anna E. Jeffreys, Christina Hubbart, Kate Rowlands, Alison T. Isaacs, Dushyanth Jyothi, Cinzia Malangone, Maryam Kamali
Article
Multidisciplinary Sciences
Luke Kemp, David C. Aldridge, Olaf Booy, Hilary Bower, Des Browne, Mark Burgmann, Austin Burt, Andrew A. Cunningham, Malcolm Dando, Jaimie T. A. Dick, Christopher Dye, Sam Weiss Evans, Belinda Gallardo, H. Charles J. Godfray, Ian Goodfellow, Simon Gubbins, Lauren A. Holt, Kate E. Jones, Hazem Kandil, Phillip Martin, Mark McCaughan, Caitriona McLeish, Thomas Meany, Kathryn Millett, Sean S. OhEigeartaigh, Nicola J. Patron, Catherine Rhodes, Helen E. Roy, Gorm Shackelford, Derek Smith, Nicola Spence, Helene Steiner, Lalitha S. Sundaram, Silja Voeneky, John R. Walker, Harry Watkins, Simon Whitby, James Wood, William J. Sutherland
Summary: Multiple national and international trends and drivers are reshaping the meaning of biological security for the United Kingdom. The UK Biological Security Strategy recognizes the importance of research in this field, and a structured approach involving expert elicitation has identified 80 policy-relevant research questions to guide future efforts in biological security.
Article
Genetics & Heredity
Andrew Hammond, Xenia Karlsson, Ioanna Morianou, Kyros Kyrou, Andrea Beaghton, Matthew Gribble, Nace Kranjc, Roberto Galizi, Austin Burt, Andrea Crisanti, Tony Nolan
Summary: Research has shown that alternative germline regulatory sequences can enhance the effectiveness of gene drives and reduce the propensity for resistant mutations, highlighting the importance of nuclease expression regulation in developing robust homing-based gene drives for population suppression.
Article
Infectious Diseases
John B. Connolly, John D. Mumford, Silke Fuchs, Geoff Turner, Camilla Beech, Ace R. North, Austin Burt
Summary: Population suppression gene drive using CRISPR-Cas9 technology has shown promising results in controlling malaria vectors. The study identified potential risks and developed risk hypotheses for simulated field releases of a transgene in West Africa, emphasizing the importance of further research and modeling to evaluate the potential harms and benefits of this approach.
Article
Biochemistry & Molecular Biology
Tin-Yu J. Hui, Jon Hael Brenas, Austin Burt
Summary: The study extends current methods for estimating contemporary effective population size by allowing the use of multiple linked loci to provide more accurate results. By deriving the covariance of changes in allele frequency at linked loci to account for between-locus correlation-induced extra sampling variance, the new method ensures reliability and accuracy in estimating Ne.
MOLECULAR ECOLOGY RESOURCES
(2021)
Article
Genetics & Heredity
Samantha M. O'Loughlin, Annie J. Forster, Silke Fuchs, Tania Dottorini, Tony Nolan, Andrea Crisanti, Austin Burt
Summary: The study identified a large number of conserved DNA sequences in Anopheles genomes with potential value for selecting and testing new targets for gene-drive modification in mosquitoes that transmit malaria.
G3-GENES GENOMES GENETICS
(2021)
Article
Genetics & Heredity
Katie Willis, Austin Burt
Summary: Synthetic gene drive systems offer efficient interventions for controlling disease vectors and pest species. It is possible to restrict the spread of gene drives by exploiting sequence differences between target and non-target populations. Double drive designs can be particularly effective for localized genetic control when there is genetic differentiation between populations.
Article
Genetics & Heredity
Silke Fuchs, William T. Garrood, Anna Beber, Andrew Hammond, Roberto Galizi, Matthew Gribble, Giulia Morselli, Tin-Yu J. Hui, Katie Willis, Nace Kranjc, Austin Burt, Andrea Crisanti, Tony Nolan, Harmit S. Malik
Summary: Gene drives have the potential to control disease-transmitting mosquitoes, but resistance and high conservation sequences can impact their efficacy. Studies have shown significant variations in the tolerance to resistance of conserved sequences, indicating a need for functional validation of future gene drive target sites.
Article
Ecology
P. J. Beaghton, Austin Burt
Summary: Synthetic gene drive constructs are developed for controlling disease vectors and pest species, but the impact of spatial processes, such as low-density-induced inbreeding and inbreeding depression, on gene drive effectiveness is critical.
THEORETICAL POPULATION BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Bhavin S. Khatri, Austin Burt
Summary: Evolution of resistance is a major barrier to the successful deployment of gene-drive systems. Multiplexed guide RNAs (gRNAs) that require resistance mutations at all target cut sites are a promising strategy to combat resistance. Research findings suggest that weakly deleterious naturally occurring variants greatly increase the probability of multisite resistance. This study provides design criteria for developing antiresistance multiplexed systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Rene Geci, Katie Willis, Austin Burt
Summary: The sterile insect technique (SIT) is not practical for controlling many pest species due to the large number of individuals needed. Previous computer models have shown that releasing males carrying a gene editor on their Y chromosome could be more efficient than SIT. This study proposes a self-propagating double drive design to further improve control efficiency. Modelling results show that this design can effectively suppress populations even with low release rates and low homing rates.
Review
Infectious Diseases
Rita Mwima, Tin-Yu J. Hui, Ann Nanteza, Austin Burt, Jonathan K. Kayondo
Summary: This study assessed the dynamics of malaria vector persistence and examined the hypotheses of aestivation, local refugia, and migration in sub-Saharan Africa. The results were inconclusive due to method limitations, such as low recapture rate in Mark-Release-Recapture method and uncertainty about conventional sampling methods. Further investigations using controlled experiments and genetic approaches are recommended to complement each other. This review unveils uncertainties and provides recommendations for future studies on malaria vector persistence mechanisms.