Publications
19 results found
D'Amato R, Taxiarchi C, Galardini M, et al., 2024, Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages., Nat Commun, Vol: 15
CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting gene drive was able to suppress laboratory Anopheles mosquito populations in 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 suggest that systems able to modulate or revert the action of gene drives, could be part of post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive to inhibit gene drive spread in age-structured Anopheles gambiae population under complex feeding and behavioural conditions. A stochastic model predicts the experimentally-observed genotype dynamics in age-structured populations in medium-sized cages and highlights the necessity of large-sized cage trials. These experiments and experimental-modelling framework demonstrate the effectiveness of the anti-drive in different scenarios, providing further corroboration for its use in controlling the spread of gene drive in Anopheles.
Hammond A, Pollegioni P, Persampieri T, et al., 2021, Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field., Nature Communications, Vol: 12, Pages: 1-9, ISSN: 2041-1723
CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings.Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.
Garrood WT, Kranjc N, Petri K, et al., 2021, Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 118, ISSN: 0027-8424
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- Citations: 16
Annas GJ, Beisel CL, Clement K, et al., 2021, A Code of Ethics for Gene Drive Research, CRISPR JOURNAL, Vol: 4, ISSN: 2573-1599
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- Citations: 16
Simoni A, Hammond AM, Beaghton AK, et al., 2020, A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae, Nature Biotechnology, Vol: 38, Pages: 1054-1060, ISSN: 1087-0156
Only female insects transmit diseases such as malaria, dengue and Zika; therefore, control methods that bias the sex ratio of insect offspring have long been sought. Genetic elements such as sex-chromosome drives can distort sex ratios to produce unisex populations that eventually collapse, but the underlying molecular mechanisms are unknown. We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae. We induced super-Mendelian inheritance of the X-chromosome-shredding I-PpoI nuclease by coupling this to a CRISPR-based gene drive inserted into a conserved sequence of the doublesex (dsx) gene. In modeling of invasion dynamics, SDGD was predicted to have a quicker impact on female mosquito populations than previously developed gene drives targeting female fertility. The SDGD at the dsx locus led to a male-only population from a 2.5% starting allelic frequency in 10-14 generations, with population collapse and no selection for resistance. Our results support the use of SDGD for malaria vector control.
Simoni A, Hammond AM, Beaghton AK, et al., 2020, A male-biased sex-distorter gene drive for the human malaria vector <i>Anopheles gambiae</i> (vol 14, pg 931, 2020), NATURE BIOTECHNOLOGY, Vol: 38, Pages: 1097-1097, ISSN: 1087-0156
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- Citations: 3
Hammond A, Galizi R, Kyrou K, et al., 2016, A CRISPR-Cas9 gene drive system-targeting female reproduction in the malaria mosquito vector Anopheles gambiae, Nature Biotechnology, Vol: 34, Pages: 78-83, ISSN: 1087-0156
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
Dritsou V, Topalis P, Windbichler N, et al., 2015, A draft genome sequence of an invasive mosquito: an Italian <i>Aedes</i> <i>albopictus</i>, PATHOGENS AND GLOBAL HEALTH, Vol: 109, Pages: 207-220, ISSN: 2047-7724
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- Citations: 25
Simoni A, Siniscalchi C, Chan YS, et al., 2015, Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster (vol 42, pg 7461, 2014), NUCLEIC ACIDS RESEARCH, Vol: 43, Pages: 2991-2991, ISSN: 0305-1048
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- Citations: 1
Simoni A, Siniscalchi C, Chan Y-S, et al., 2014, Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster, Nucleic Acids Research, Vol: 42, Pages: 7461-7472, ISSN: 1362-4962
Selfish genes are DNA elements that increase their rate of genetic transmission at the expense of other genes in the genome and can therefore quickly spread within a population. It has been suggested that selfish elements could be exploited to modify the genome of entire populations for medical and ecological applications. Here we report that transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) can be engineered into site-specific synthetic selfish elements (SSEs) and demonstrate their transmission of up to 70% in the Drosophila germline. We show here that SSEs can spread via DNA break-induced homologous recombination, a process known as ‘homing’ similar to that observed for homing endonuclease genes (HEGs), despite their fundamentally different modes of DNA binding and cleavage. We observed that TALEN and ZFN have a reduced capability of secondary homing compared to HEG as their repetitive structure had a negative effect on their genetic stability. The modular architecture of ZFNs and TALENs allows for the rapid design of novel SSEs against specific genomic sequences making them potentially suitable for the genetic engineering of wild-type populations of animals and plants, in applications such as gene replacement or population suppression of pest species.
Simoni A, Wolfgang W, Topping MP, et al., 2014, A Mechanosensory Pathway to the <i>Drosophila</i> Circadian Clock, Science, Vol: 343, Pages: 525-528, ISSN: 0036-8075
<jats:title>Coordinating the Clock</jats:title> <jats:p> In flies, the mechanosensory chordotonal organs help to coordinate the effects of temperature on circadian cycles. <jats:bold> Simoni <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6170" page="525" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1245710">525</jats:related-article> ) provide a mechanism by which mechanosensory input is processed to help to synchronize the biological clock in <jats:italic>Drosophila melanogaster</jats:italic> . The chordotonal organs, which have similarities to the mammalian ear, were also required for sensation of a vibration stimulus and its effects on the endogenous brain clock. The chordotonal organs, present in the joints of the limbs, provide neuronal signals that allow the animal to sense its position or posture—and thus might mediate feedback of a range of behaviors onto the endogenous biological clock. </jats:p>
Simoni A, Siniscalchi C, Chan YS, et al., 2013, DEVELOPMENT OF NOVEL SYNTHETIC SELFISH ELEMENTS FOR POPULATION ENGINEERING AND VECTOR CONTROL, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 442-442, ISSN: 2047-7724
Wolfgang W, Simoni A, Gentile C, et al., 2013, The Pyrexia transient receptor potential channel mediates circadian clock synchronization to low temperature cycles in <i>Drosophila melanogaster</i>, Proceedings of the Royal Society B: Biological Sciences, Vol: 280, Pages: 20130959-20130959, ISSN: 0962-8452
<jats:p> Circadian clocks are endogenous approximately 24 h oscillators that temporally regulate many physiological and behavioural processes. In order to be beneficial for the organism, these clocks must be synchronized with the environmental cycles on a daily basis. Both light : dark and the concomitant daily temperature cycles (TCs) function as <jats:italic>Zeitgeber</jats:italic> (‘time giver’) and efficiently entrain circadian clocks. The temperature receptors mediating this synchronization have not been identified. Transient receptor potential (TRP) channels function as thermo-receptors in animals, and here we show that the Pyrexia (Pyx) TRP channel mediates temperature synchronization in <jats:italic>Drosophila melanogaster</jats:italic> . Pyx is expressed in peripheral sensory organs (chordotonal organs), which previously have been implicated in temperature synchronization. Flies deficient for Pyx function fail to synchronize their behaviour to TCs in the lower range (16–20°C), and this deficit can be partially rescued by introducing a wild-type copy of the <jats:italic>pyx</jats:italic> gene. Synchronization to higher TCs is not affected, demonstrating a specific role for Pyx at lower temperatures. In addition, <jats:italic>pyx</jats:italic> mutants speed up their clock after being exposed to TCs. Our results identify the first TRP channel involved in temperature synchronization of circadian clocks. </jats:p>
Gentile C, Sehadova H, Simoni A, et al., 2013, Cryptochrome Antagonizes Synchronization of Drosophila’s Circadian Clock to Temperature Cycles, Current Biology, Vol: 23, Pages: 185-195, ISSN: 0960-9822
Wolfgang W, Simoni A, Joerg AT, et al., 2012, Synchronization of the <i>Drosophila</i> circadian clock by temperature, humidity and mechanical stimulation, JOURNAL OF NEUROGENETICS, Vol: 26, Pages: 12-13, ISSN: 0167-7063
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- Citations: 1
Simoni A, Stanewsky R, 2010, The DN2 clock neurons regulate period and phase of eclosion rhythms during temperature entrainment, JOURNAL OF NEUROGENETICS, Vol: 24, Pages: 26-26, ISSN: 0167-7063
Wolfgang W, Gentile C, Simoni A, et al., 2010, Trp-channels affect temperature entrainment of the circadian clock in <i>Drosophila melanogaster</i>, JOURNAL OF NEUROGENETICS, Vol: 24, Pages: 55-56, ISSN: 0167-7063
Sehadova H, Glaser FT, Gentile C, et al., 2009, Temperature Entrainment of <i>Drosophila</i>'s Circadian Clock Involves the Gene <i>nocte</i> and Signaling from Peripheral Sensory Tissues to the Brain, NEURON, Vol: 64, Pages: 251-266, ISSN: 0896-6273
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- Citations: 112
Glaser F, Sehadova H, Giesecke A, et al., 2009, Temperature entrainment mechanisms in <i>Drosophila</i> involve the novel gene <i>nocte</i> and peripheral organ to brain signaling, JOURNAL OF NEUROGENETICS, Vol: 23, Pages: S50-S50, ISSN: 0167-7063
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