Keywords: Replicator/site directed nuclease

A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

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Hou S, Chen J, Feng R, Xu X, Liang N, Champer J.,  Journal of Genetics and Genomics,  2024.
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 the desired gene construct throughout ...

Manipulating the Destiny of Wild Populations Using CRISPR

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Raban R, Marshall JM, Hay BA, Akbari OS.,  Annual Reviews,  57:361-390. 2023.
Genetic biocontrol aims to suppress or modify populations of species to protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge in research in this field, with one gene editing technology, CRISPR, leading the ...

Gene drives for invasive wasp control: Extinction is unlikely, with suppression dependent on dispersal and growth rates

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P. J. Lester, D. O'Sullivan and G. L. W. Perry,  Ecological Applications,  2023.
Abstract Gene drives offer a potentially revolutionary method for pest control over large spatial extents. These genetic modifications spread deleterious variants through a population and have been proposed as methods for pest suppression or even eradication. We examined the ...

CRISPR/Cas9-Based Gene Drive Could Suppress Agricultural Pests

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M. Kulikowski,  Current Science Daily,  2023.
Researchers have developed a “homing gene drive system” based on CRISPR/Cas9 that could be used to suppress populations of Drosophila suzukii vinegar flies – so-called “spotted-wing Drosophila” that devastate soft-skinned fruit in North America, Europe and parts of ...

New germline Cas9 promoters show improved performance for homing gene drive

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D. Jie, C. Weizhe, J. Xihua, X. Xuejiao, Y. Emily, Z. Ruizhi, Z. Yuqi, M. Matt, W. M. Philipp and C. Jackson,  bioRxiv,  2023.07.16.549205. 2023.
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives, perhaps the most powerful gene drive strategy, convert wild type alleles ...

Guerrilla eugenics: gene drives in heritable human genome editing

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A. D. Cutter,  J Med Ethics,  2023.
CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome ...

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

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T. Harvey-Samuel, X. Feng, E. M. Okamoto, D.-K. Purusothaman, P. T. Leftwich, L. Alphey and V. M. Gantz,  bioRxiv,  2023.06.12.544656. 2023.
Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes ...

CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii

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A. K. Yadav, C. Butler, A. Yamamoto, A. A. Patil, A. L. Lloyd and M. J. Scott,  Proc Natl Acad Sci U S A,  120:e2301525120. 2023.
Genetic-based methods offer environmentally friendly species-specific approaches for control of insect pests. One method, CRISPR homing gene drive that target genes essential for development, could provide very efficient and cost-effective control. While significant progress has ...

CRISPR-based gene editing of non-homologous end joining factors biases DNA repair pathway choice toward single-strand annealing in Aedes aegypti

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K. Chae, J. M. Overcash, C. Dawson, C. Valentin, H. Tsujimoto, K. M. Myles and Z. N. Adelman,  Current Research in Biotechnology,  5:100133. 2023.
To maintain genome stability, eukaryotic cells orchestrate DNA repair pathways to process DNA double-strand breaks (DSBs) that result from diverse developmental or environmental stimuli. Bias in the selection of DSB repair pathways, either non-homologous end joining (NHEJ) or ...

Rapid, scalable, combinatorial genome engineering by marker-less enrichment and recombination of genetically engineered loci in yeast

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M. Abdullah, B. M. Greco, J. M. Laurent, R. K. Garge, D. R. Boutz, M. Vandeloo, E. M. Marcotte and A. H. Kachroo,  Cell Rep Methods,  3:100464. 2023.
A major challenge to rationally building multi-gene processes in yeast arises due to the combinatorics of combining all of the individual edits into the same strain. Here, we present a precise and multi-site genome editing approach that combines all edits without selection ...

Evolution driven by genetic engineering should be known as ‘genetic welding’ to draw scientific and ethical scrutiny

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S. Moore,  AZO Life Sciences,  2023.
The advent of CRISPR-Cas9 technology has been revolutionary, but it has also been highly controversial. In an opinion paper published in the journal Trends in Genetics, evolutionary geneticist Asher Cutter highlights the importance of coining the term ‘genetic welding’ for ...

Next-generation CRISPR gene-drive systems using Cas12a nuclease

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S. Sanz Juste, E. M. Okamoto, X. Feng and V. L. Del Amo,  bioRxiv,  2023.02.20.529271. 2023.
One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a ...

The Possibilities of Gene Drives for Managing Populations and Controlling Diseases

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J. Vijay Upadhye, U. N. Shah and B. Mudhol,  Salud, Ciencia y Tecnologia,  3. 2023.
The technical limitations and the use of gene drives to address ecological problems by modifying all populations of wild species remain primarily speculative. Here, we examine the possibility that RNA-guided gene drives based on the CRISPR nuclease Cas9 could be used as an ...

A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

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S. A. N. Verkuijl, E. Gonzalez, M. Li, J. X. D. Ang, N. P. Kandul, M. A. E. Anderson, O. S. Akbari, M. B. Bonsall and L. Alphey,  Nature Communications,  13:7145. 2022.
CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing drives are designed to replace a wild-type allele with a copy of a drive element on the homologous chromosome. In Aedes aegypti, the sex-determining locus is closely linked to the white ...

Modeling the efficacy of CRISPR gene drive for snail immunity on schistosomiasis control

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R. E. Grewelle, J. Perez-Saez, J. Tycko, E. K. O. Namigai, C. G. Rickards and G. A. De Leo,  PLOS Neglected Tropical Diseases,  16:e0010894. 2022.
CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. Gene drive technology in mollusks has received little attention despite the role of freshwater snails as ...

Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single generation crosses and modeling

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W. Reid, A. E. Williams, I. Sanchez-Vargas, J. Lin, R. Juncu, K. E. Olson and A. W. E. Franz,  G3 Genes|Genomes|Genetics,  2022.
Critical to the design of a single-locus autonomous GD is that the selected genomic locus is amenable to both GD and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target two intergenic genomic loci, which had previously shown to be ...

Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure

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S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer,  eLife,  11:e79121. 2022.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter ...

A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation

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B. S. Khatri and A. Burt,  Proceedings of the National Academy of Sciences,  119:e2200567119. 2022.
CRISPR-based gene drives have the potential for controlling natural populations of disease vectors, such as malaria-carrying mosquitoes in sub-Saharan Africa. If successful, they hold promise of significantly reducing the burden of disease and death from malaria and many other ...

Development of CRISPR/Cas9-Mediated Gene-Drive Construct Targeting the Phenotypic Gene in Plutella xylostella

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M. Asad, D. Liu, J. Li, J. Chen and G. Yang,  Frontiers in Physiology,  13:938621. 2022.
The gene-drive system can ensure that desirable traits are transmitted to the progeny more than the normal Mendelian segregation. The clustered regularly interspersed palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated gene-drive system has been demonstrated ...

A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes

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E. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois,  bioRxiv,  2022.07.08.499187. 2022.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria ...

Genetic Approaches for Controlling CRISPR-based Autonomous Homing Gene Drives

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P. R. Chennuri, Z. N. Adelman and K. M. Myles,  Frontiers in Bioengineering and Biotechnology,  10:897231. 2022.
CRISPR-based autonomous homing gene drives are a potentially transformative technology with the power to reduce the prevalence of, or even eliminate, vector-borne diseases, agricultural pests, and invasive species. However, there are a number of regulatory, ethical, ...

Experimental demonstration of tethered gene drive systems for confined population modification or suppression

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M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer,  BMC Biol,  20:119. 2022.
BACKGROUND: Homing gene drives hold great promise for the genetic control of natural populations. However, current homing systems are capable of spreading uncontrollably between populations connected by even marginal levels of migration. This could represent a substantial ...

Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

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A. L. Bishop, V. López Del Amo, E. M. Okamoto, Z. Bodai, A. C. Komor and V. M. Gantz,  Nat Commun,  13:2595. 2022.
Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the ...

Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models

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Y. Liu, W. Teo, H. Yang and J. Champer,  bioRxiv,  2022.05.08.491087. 2022.
Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be ...

Experimental demonstration of tethered gene drive systems for confined population modification or suppression

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M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2021.05.29.446308. 2022.
Homing gene drives hold great promise for the genetic control of natural populations. However, current homing systems are capable of spreading uncontrollably between populations connected by even marginal levels of migration. This could represent a substantial sociopolitical ...

Gene drive escape from resistance depends on mechanism and ecology

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F. Cook, J. J. Bull and R. Gomulkiewicz,  Evolutionary Applications,  2022.
Abstract Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether antidrive resistance will evolve ...

Modelling homing suppression gene drive in haplodiploid organisms

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Y. Liu and J. Champer,  Proceedings of the Royal Society B: Biological Sciences,  289:20220320. 2022.
Gene drives have shown great promise for suppression of pest populations.These engineered alleles can function by a variety of mechanisms, but themost common is the CRISPR homing drive, which converts wild-type allelesto drive alleles in the germline of heterozygotes. Some ...

Cas9-mediated maternal-effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae

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R. Carballar-Lejarazú, T. Tushar, T. B. Pham and A. A. James,  Genetics,  2022.
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 ...

Toward a CRISPR-Cas9-Based Gene Drive in the Diamondback Moth Plutella xylostella

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X. Xu, T. Harvey-Samuel, H. A. Siddiqui, J. X. D. Ang, M. E. Anderson, C. M. Reitmayer, E. Lovett, P. T. Leftwich, M. You and L. Alphey,  The CRISPR Journal,  5:224-236. 2022.
Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipteran insects, yeast, and mice for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. ...

Finding the strongest gene drive: Simulations reveal unexpected performance differences between Anopheles homing suppression drive candidates

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S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2022.03.28.486009. 2022.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter ...

Modelling homing suppression gene drive in haplodiploid organisms

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Y. Liu and J. Champer,  bioRxiv,  2021.10.12.464047. 2022.
Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some ...

Considerations for homology-based DNA repair in mosquitoes: Impact of sequence heterology and donor template source

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J. X. D. Ang, K. Nevard, R. Ireland, D.-K. Purusothaman, S. A. N. Verkuijl, L. Shackleford, E. Gonzalez, M. A. E. Anderson and L. Alphey,  PLOS Genetics,  18:e1010060. 2022.
Author summary The field of genetic control of mosquito vectors has progressed rapidly in recent years, especially in Cas9-based control systems, due to its robustness to elicit a species-specific and dispersive control of mosquito population. To generate a Cas9-based ...

Gene-drive mosquitoes, a prospect for future malaria control

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S. A. Monawwer, A. O. I. Alzubaidi, F. Yasmin, S. M. Q. Haimour, S. M. I. Shay and I. Ullah,  Pan African Medical Journal,  41:2-6. 2022.
Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and ...

Gene drives for vertebrate pest control: realistic spatial modelling of eradication probabilities and times for island mouse populations

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A. Birand, P. Cassey, J. V. Ross, J. C. Russell, P. Thomas and T. A. A. Prowse,  Molecular Ecology,  2022.
Abstract Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used to suppress or eradicate pest populations. We develop an individual-based, ...

Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework

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S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer,  PLoS Comput Biol,  17:e1009660. 2021.
Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among ...

Modeling impact and cost-effectiveness of driving-Y gene drives for malaria elimination in the Democratic Republic of the Congo

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N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin,  Evolutionary Applications,  2021.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a ...

Demographic feedbacks can hamper the spatial spread of a gene drive

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L. Girardin and F. Débarre,  Journal of Mathematical Biology,  83:67. 2021.
This paper is concerned with a reaction–diffusion system modeling the fixation and the invasion in a population of a gene drive (an allele biasing inheritance, increasing its own transmission to offspring). In our model, the gene drive has a negative effect on the fitness of ...

Gene drives and population persistence vs elimination: the impact of spatial structure and inbreeding at low density

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P. J. Beaghton and A. Burt,  bioRxiv,  2021.11.11.468225. 2021.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same ...

Modeling homing suppression gene drive in haplodiploid organisms

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Y. Liu and J. Champer,  bioRxiv,  2021.10.12.464047. 2021.
Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some ...

Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation

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S. Fuchs, W. T. Garrood, A. Beber, A. Hammond, R. Galizi, M. Gribble, G. Morselli, T.-Y. J. Hui, K. Willis, N. Kranjc, A. Burt, A. Crisanti and T. Nolan,  PLOS Genetics,  17. 2021.
Author summary Gene drives have the potential to be applied as a novel control strategy of disease-transmitting mosquitoes, by spreading genetic traits that suppress or modify the target population. Many gene drive elements work by recognising and cutting a specific target ...

Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation

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S. Fuchs, W. Garrood, A. Beber, A. Hammond, R. Galizi, M. Gribble, G. Morselli, T.-Y. Hui, K. Willis, N. Kranjc, A. Burt, T. Nolan and A. Crisanti,  bioRxiv,  2021.
CRISPR-based homing gene drives can be designed to disrupt essential genes whilst biasing their own inheritance, leading to suppression of mosquito populations in the laboratory. This class of gene drives relies on CRISPR-Cas9 cleavage of a target sequence and copying ...

Targeting Conserved Sequences Circumvents the Evolution of Resistance in a Viral Gene Drive against Human Cytomegalovirus

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M. Walter, R. Perrone, E. Verdin and F. Goodrum,  Journal of Virology,  95:e00802-21. 2021.
Gene drives are genetic systems designed to efficiently spread a modification through a population. They have been designed almost exclusively in eukaryotic species, especially in insects. We recently developed a CRISPR-based gene drive system in herpesviruses that relies on ...

Autocatalytic-protection for an unknown locus CRISPR-Cas countermeasure for undesired mutagenic chain reactions

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E. Schonfeld, E. Schonfeld and D. Schonfeld,  Journal of Theoretical Biology,  528:110831. 2021.
The mutagenic chain reaction (MCR) is a genetic tool to use a CRISPR–Cas construct to introduce a homing endonuclease, allowing gene drive to influence whole populations in a minimal number of generations (Esvelt et al., 2014, Gantz and Bier, 2015, Gantz and Bier, 2016). The ...

Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito

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W. T. Garrood, N. Kranjc, K. Petri, D. Y. Kim, J. A. Guo, A. M. Hammond, I. Morianou, V. Pattanayak, J. K. Joung, A. Crisanti and A. Simoni,  Proceedings of the National Academy of Sciences,  118:e2004838117. 2021.
CRISPR-Cas9 nuclease-based gene drives have been developed toward the aim of control of the human malaria vector Anopheles gambiae. Gene drives are based on an active source of Cas9 nuclease in the germline that promotes super-Mendelian inheritance of the transgene by ...

Experimental demonstration of tethered gene drive systems for confined population modification or suppression

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M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2021.05.29.446308. 2021.
Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive. Here, we demonstrate the engineering of a ...

A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles

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E. Yang, M. Metzloff, A. M. Langmüller, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2021.05.27.446071. 2021.
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 ...

Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes

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R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James,  J Vis Exp,  2021.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. ...

Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement

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A. Hoermann, S. Tapanelli, P. Capriotti, G. Del Corsano, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler,  eLife,  10. 2021.
Gene drives for mosquito population replacement are promising tools for malaria control. However, there is currently no clear pathway for safely testing such tools in endemic countries. The lack of well-characterized promoters for infection-relevant tissues and regulatory hurdles ...

Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control

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S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt,  G3-Genes Genomes Genetics,  2021.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were ...

Evading resistance to gene drives

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R. Gomulkiewicz, M. L. Thies and J. J. Bull,  Genetics,  217. 2021.
Here, we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially. Previous models assumed resistance is allelic to the drive. We relax this assumption and show that linkage ...

Gene-Editing Approach To Control the Invasive Gray Squirrel

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M. Campbell,  Technology Networks,  2021.
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently ...

A confinable home and rescue gene drive for population modification

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N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. S. Akbari,  eLife,  10:e65939. 2021.
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population ...

Ecology: Gene drives may help control invasive grey squirrel in the UK

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A. Korn,  EurekaAlert,  2021.
Gene drives introduce genes into a population that have been changed to induce infertility in females, allowing for the control of population size. However, they face technical challenges, such as controlling the spread of altered genes as gene drive individuals mate with wild ...

Genetically modified squirrels could curb growing population of greys

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S. Knapton,  Telegraph,  2021.
Mutant grey squirrels, genetically modified to spread infertility genes, could be released into the wild to tackle the burgeoning population,

Expert reaction to a paper suggesting that gene drives could be used to help control grey squirrel numbers in the UK

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Anonymous,  Science Media Centre,  2021.
This study assesses the prospects for using a gene drive to control invasive grey squirrels in the UK. This is a modelling study exploring the potential for such an approach – no such gene drives currently exist and developing them for grey squirrels would be quite a long-term ...

CRISPR gene drives may come to a squirrel near you.

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Anonymous,  NewsBeezer,  2021.
Today’s gene drive technologies could be blended to provide control of the invasive gray squirrel population in the UK – with minimal risk to other populations, according to a new modeling published in the journal Scientific reports. Gene driving introduces altered genes ...

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

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N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc,  Scientific Reports,  11:3719. 2021.
As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene ...

Designing gene drives to limit spillover to non-target populations

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G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim,  PLOS Genetics,  17:e1009278. 2021.
We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population ...

Modeling impact and cost-effectiveness of gene drives for malaria elimination in the Democratic Republic of the Congo

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N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin,  medRxiv,  2020.06.29.20142760. 2021.
Using a spatially explicit, agent-based model of malaria transmission in eight representative provinces of the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that ...

Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance

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A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan,  PLOS Genetics,  17:e1009321. 2021.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.

Control of malaria-transmitting mosquitoes using gene drives

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T. Nolan,  Philosophical Transactions of the Royal Society B: Biological Sciences,  376:20190803. 2020.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne ...

A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias

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S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey,  bioRxiv,  2020.12.15.421271. 2020.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. ...

Evading resistance to gene drives

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R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.08.27.270611. 2020.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered ...

Split drive killer-rescue provides a novel threshold-dependent gene drive

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M. P. Edgington, T. Harvey-Samuel and L. Alphey,  Scientific Reports,  10. 2020.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given ...

Evading evolution of resistance to gene drives

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R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.08.27.270611. 2020.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of this type would achieve only partial population suppression, but multiple drives (perhaps delivered ...

Gene Drive: The What, How, Why, and Whether We Should

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N. Pazhayam,  The Pipettepen,  2020.
Under regular Mendelian inheritance, the probability of inheriting a particular allele from a heterozygous parent is 50% – this is because offspring can only inherit one or the other chromosome from each parent. However, gene drive is a technology that changes this probability ...

Progress Toward Zygotic and Germline Gene Drives in Mice

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C. Pfitzner, M. A. White, S. G. Piltz, M. Scherer, F. Adikusuma, J. N. Hughes and P. Q. Thomas,  The CRISPR Journal,  3:388-397. 2020.
Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing "split drive" systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter.

MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics

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S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall,  bioRxiv,  2020.10.16.343376. 2020.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.

Engineered Gene Drives: State of Research Webinar Series by The GeneConvene Global Collaborative September-October 2020

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David O'Brochta and Hector Quemada,  GeneConvene Global Collaborative,  2020.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.

Engineering the Composition and Fate of Wild Populations with Gene Drive

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B. A. Hay, G. Oberhofer and M. Guo,  Annual Review of Entomology,  2020.
We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.

Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control

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M. P. Su, M. Georgiades, J. Bagi, K. Kyrou, A. Crisanti and J. T. Albert,  Parasites and Vectors,  13:507. 2020.
We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages.

Viral gene drive in herpesviruses

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M. Walter and E. Verdin,  Nature Communications,  11:4884. 2020.
Here, we report on a gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses.

Gene Drive Control Worry Eased by Genetic Neutralizing Elements

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Staff,  Genetic Engineering and Biotechnology News,  2020.
Bier and his colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild, offering two new solutions based on elements developed in the common fruit fly. T

Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives

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X.-R. S. Xu, E. A. Bulger, V. M. Gantz, C. Klanseck, S. R. Heimler, A. Auradkar, J. B. Bennett, L. A. Miller, S. Leahy, S. S. Juste, A. Buchman, O. S. Akbari, J. M. Marshall and E. Bier,  Molecular Cell,  2020.
Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs).

Biologists create new genetic systems to neutralize gene drives

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University of California San Diego,  ScienceDaily,  2020.
Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild.

A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population

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J. Champer, E. Yang, E. Lee, J. Liu, A. G. Clark and P. W. Messer,  Proceedings of the National Academy of Sciences,  202004373. 2020.
Here, we present a CRISPR homing drive that was able to successfully spread to all individuals in a laboratory cage study in Drosophila melanogaster without any apparent evolution of resistance.

Inherently confinable split-drive systems in Drosophila

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G. Terradas, A. B. Buchman, J. B. Bennett, I. Shriner, J. M. Marshall, O. S. Akbari and E. Bier,  bioRxiv,  2020.09.03.282079. 2020.
Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that were inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). I

Evading evolution of resistance to gene drives

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R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

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N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc,  bioRxiv,  2020.
We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and ...

Anthony James / Mosquito Modification

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Big Picture Science,  SETI Institute,  2020.
Anthony James, vector biologist at the University of California, Irvine, describeshow we might genetically modify mosquitoes to make them unable to pass malaria on to humans.

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

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R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James,  Proceedings of the National Academy of Sciences,  202010214. 2020.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.

A home and rescue gene drive forces its inheritance stably persisting in populations

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N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. Akbari,  bioRxiv,  2020.08.21.261610. 2020.
We demonstrate that HomeR can achieve nearly ~100% transmission enabling it to persist at genotypic fixation in several multi-generational population cage experiments, underscoring its long term stability.

Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility

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A. R. North, A. Burt and H. C. J. Godfray,  BMC Biology,  18:98. 2020.
Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. Here, ...

CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain

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J. Champer,  Genetic Literacy Project,  2020.
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, ...

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

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A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James,  bioRxiv,  2020.08.02.233056. 2020.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional ...

Chemical controllable gene drive in Drosophila

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D. Chae, J. Lee, N. Lee, K. Park, S. J. Moon and H. H. Kim,  ACS Synthetic Biology,  in press. 2020.
Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted ...

Can a population targeted by a CRISPR-based homing gene drive be rescued?

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N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  G3-Genes Genomes Genetics,  2020.
N. O. Rode, V. Courtier-Orgogozo and F. Débarre (2020). G3 doi: 10.1534/g3.120.401484 Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals ...

Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives

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V. López Del Amo, B. S. Leger, K. J. Cox, S. Gill, A. L. Bishop, G. D. Scanlon, J. A. Walker, V. M. Gantz and A. Choudhary,  Cell Reports,  31:107841. 2020.
Summary Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of ...

Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes

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P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller,  Journal of Applied Ecology,  11. 2020.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this ...

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

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A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti,  Nature Biotechnology,  2020.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.

Gene drive outcomes not determined by genetic variation – A Podcast

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Thomas Locke,  Malaria Minute,  2020.
Gene drives are a system of genetic modification that use ‘molecular scissors’ to edit DNA sequences that self-perpetuate to ensure the rapid spread of mutation in a population. They offer new avenues for eradicating vector-borne diseases like malaria. They rely on the Cas9 ...

The yeast mating-type switching endonuclease HO is a domesticated member of an unorthodox homing genetic element family

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A. Y. Coughlan, L. Lombardi, S. Braun-Galleani, A. A. R. Martos, V. Galeote, F. Bigey, S. Dequin, K. P. Byrne and K. H. Wolfe,  eLife,  9:e55336. 2020.
The mating-type switching endonuclease HO plays a central role in the natural life cycle of Saccharomyces cerevisiae, but its evolutionary origin is unknown. HO is a recent addition to yeast genomes, present in only a few genera close to Saccharomyces. Here we show that HO is ...

Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline

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H. A. Grunwald, V. M. Gantz, G. Poplawski, X.-r. S. Xu, E. Bier and K. L. Cooper,  TAGC 2020,  2020.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems that have recently been developed in insects, which leverage the sequence-targeted DNA cleavage ...

Strategies for Achieving Gene Drive – Over-Replication

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GeneConvene Global Collaborative,  GeneConvene Global Collaborative,  2020.

Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs

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S. E. Champer, S. Y. Oh, C. Liu, Z. Wen, A. G. Clark, P. W. Messer and J. Champer,  Science Advances,  6:eaaz0525. 2020.
The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, ...

Performance analysis of novel toxin-antidote CRISPR gene drive systems

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J. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer,  BMC Biology,  18:27. 2020.
CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. ...

Gene technologies in weed management: a technical feasibility analysis

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N. Kumaran, A. Choudhary, M. Legros, A. W. Sheppard, L. G. Barrett, D. M. Gardiner and S. Raghu,  Current Opinion in Insect Science,  38:6-14. 2020.
With the advent of new genetic technologies such as gene silencing and gene drive, efforts to develop additional management tools for weed management is gaining significant momentum. These technologies promise novel ways to develop sustainable weed control options because gene ...

A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

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V. López Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  Nature Communications,  11:352. 2020.
CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and ...

Assessment of a Split Homing Based Gene Drive for Efficient Knockout of Multiple Genes

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N. P. Kandul, J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari,  G3: Genes|Genomes|Genetics,  10:827-837. 2019.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host encoded genes have been identified that are important for pathogen transmission, targeting ...

The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes

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Alcalay, Y., S. Fuchs, R. Galizi, F. Bernardini, R. E. Haghighat-Khah, D. B. Rusch, J. R. Adrion, M. W. Hahn, P. Tortosa and P. A. Papathanos,  bioRxiv,  2019:860551. 2019.
Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X chromosome shredding operates through the targeted elimination of X-chromosome-bearing ...

Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O’nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain

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Mumford, J. D., C. A. Long, S. C. Weaver, K. Miura, E. Wang, R. Rotenberry, E. M. Dotson and M. Q. Benedict,  " Journal of Medical Entomology,  56:936-941. 2019.
ransgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit ...

Daisy-chain gene drives

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MIT Media Lab,  2019.

CRISPR gene drive efficiency and resistance rate is highly heritable with no common genetic loci of large effect

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Champer, JW, Z. X.; Luthra, A.; Reeves, R.; Chung, J.; Liu, C.; Lee, Y. L.; Liu, J. X.; Yang, E.; Messer, P. W.; Clark, A. G.,  Genetics,  212:333-341. 2019.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving ...

Gene Drive – Esvelt

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iBiology,  2019.
Dr. Kevin Esvelt explains how CRISPR-based gene drives can be used to spread genetic alterations through wild populations. He discusses strategies to maximize benefit and minimize risk.

Multiplexing gRNAs to Hedge Against Resistance to Gene Drive

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Travis Van Warmerdam,  IGTRCN,  2018.
Recently, Oberhofer et al (2018) published a paper examining the mechanisms of homing endonuclease gene drives in The Proceedings of the National Academy of Sciences. They used a novel nuclease-encoding cassette containing four multiplexed gRNAs targeting genes required for ...

Gene drive to reduce malaria transmission in sub-Saharan Africa

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Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K.,  Journal of Responsible Innovation,  5:S66-S80. 2018.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a ...

Selfish genetic elements

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Agren, JAC, A. G.,  PLOS Genetics,  14:20. 2018.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative ...

A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes

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Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea,  Nature Biotechnology,  36:1062–1066. 2018.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) ...

Redkmer: An assembly-free pipeline for the identification of abundant and specific X-chromosome target sequences for X-shredding by CRISPR endonucleases

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Papathanos, PAW, Nikolai,  CRISPR Journal,  1:88-98. 2018.
CRISPR-based synthetic sex ratio distorters, which operate by shredding the X-chromosome during male meiosis, are promising tools for the area-wide control of harmful insect pest or disease vector species. X-shredders have been proposed as tools to suppress insect populations by ...

Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs

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Oberhofer, GI, Tobin; Hay, Bruce A.,  Proceedings of the National Academy of Sciences of the United States of America,  115:e9343. 2018.
Homing endonuclease gene (HEG)-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage but that retain ...

Gene drive: Evolved and synthetic

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Burt, AC, Andrea,  ACS Chemical Biology,  13:343-346. 2018.
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to—or indeed even if they detract from—organismal survival and reproduction. Genetic elements that can ...

Gene Drives Explained – Questions about Gene Drives

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Question.,  2017.
Hi, thanks for watching on the channel Question, where we seek to better understand scientific breakthroughs by asking and answering questions. Today’s video topic is on gene drives - a way to increase the frequency of an allele in a population. Gene drives work hand in hand ...

Gene drive for Malaria control | Andrea Crisanti |

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TEDx,  2017.

How driving endonuclease genes can be used to combat pests and disease vectors

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Godfray, HCJN, A.; Burt, A.,  BMC Biology,  15:81. 2017.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the ...

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

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Eckhoff, PAW, E. A.; Godfray, H. C. J.; Burt, A.,  Proceedings of the National Academy of Sciences of the United States of America,  114:e255-e264. 2017.
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with ...

Gene drives do not always increase in frequency: from genetic models to risk assessment

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de Jong, TJ,  Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety,  12:299-307. 2017.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an ...

The promise and peril of CRISPR gene drives

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Zentner, GEW, Michael J. C.,  Bioessays,  39:1-9. 2017.
Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing ...

Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing

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Beaghton, AH, Andrew; Nolan, Tony; Crisanti, Andrea; Godfray, H. Charles J.; Burt, Austin,  Genetics,  205:1587-1596. 2017.
There is a need for new interventions against the ongoing burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing ...

Lethal Gene Drive Selects Inbreeding

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J. J. Bull,  bioRxiv,  046847. 2016.
ere, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in ...

Cheating evolution: engineering gene drives to manipulate the fate of wild populations

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Champer, JB, A.; Akbari, O. S.,  Nature Reviews Genetics,  17:146-159. 2016.
Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne ...

Gene drive through a landscape: Reaction-diffusion models of population suppression and elimination by a sex ratio distorter

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Beaghton, AB, P. J.; Burt, A.,  Theoretical Population Biology,  108:51-69. 2016.
Some genes or gene complexes are transmitted from parents to offsprihg at a greater-than-Mendelian rate, and can spread and persist in populations even if they cause some harm to the individuals carrying them. Such genes may be useful for controlling populations or species that ...

What is a Gene Drive?

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STAT,  STAT,  2015.

CRISPR-Cas9: Safeguarding Gene Drives

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Harvard University,  2015.

A synthetic sex ratio distortion system for the control of the human malaria mosquito

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Galizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A.,  Nature Communications,  5:3977. 2014.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has ...

Modelling the spatial spread of a homing endonuclease gene in a mosquito population

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North, AB, A.; Godfray, H. C. J.,  Journal of Applied Ecology,  50:1216-1225. 2013.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important ...

The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene drive

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Chan, YST, R.; Jarjour, J.; Huen, D. S.; Stoddard, B. L.; Russell, S.,  PLOS One,  8:e74254. 2013.
The homing endonuclease gene (HEG) drive system, a promising genetic approach for controlling arthropod populations, utilises engineered nucleases to spread deleterious mutations that inactivate individual genes throughout a target population. Previous work with a naturally ...

Optimising homing endonuclease gene drive performance in a semi-refractory species: The Drosophila melanogaster experience

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Chan, YSH, D. S.; Glauert, R.; Whiteway, E.; Russell, S.,  PLOS One,  8:e54130. 2013.
Homing endonuclease gene (HEG) drive is a promising insect population control technique that employs meganucleases to impair the fitness of pest populations. Our previous studies showed that HEG drive was more difficult to achieve in Drosophila melanogaster than Anopheles gambiae ...

Germline excision of transgenes in Aedes aegypti by homing endonucleases

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Aryan, AA, M. A. E.; Myles, K. M.; Adelman, Z. N.,  Scientific Reports,  3:1603. 2013.
Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this report, we show that the HEs Y2-I-AniI, ...

Requirements for effective malaria control with homing endonuclease genes

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Deredec, AG, H. C. J.; Burt, A.,  Proceedings of the National Academy of Sciences of the United States of America,  108:e874-e880. 2011.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally ...

Insect population control by homing endonuclease-based gene drive: An evaluation in Drosophila melanogaster

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Chan, YSN, D. A.; Huen, D. S.; Russell, S.,  Genetics,  188:33-44. 2011.
Insects play a major role as vectors of human disease as well as causing significant agricultural losses. Harnessing the activity of customized homing endonuclease genes (HEGs) has been proposed as a method for spreading deleterious mutations through populations with a view to ...

A synthetic homing endonuclease-based gene drive system in the human malaria mosquito

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Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A.,  Nature,  473:212-215. 2011.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of ...

The population genetics of using homing endonuclease genes in vector and pest management

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Deredec, AB, A.; Godfray, H. C. J.,  Genetics,  179:2013-2026. 2008.
Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double- strand breaks in the homologous chromosome at the precise position opposite the HFG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, ...

Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae

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Windbichler, NP, P. A.; Crisanti, A.,  PLOS Genetics,  4:1-9. 2008.
We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes ...

Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos

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Windbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A.,  Nucleic Acids Research,  35:5922-5933. 2007.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of ...

Degeneration and domestication of a selfish gene in yeast: Molecular evolution versus site-directed mutagenesis

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Koufopanou, VB, A.,  Molecular Biology and Evolution,  22:1535-1538. 2005.
VDE is a homing endonuclease gene in yeasts with an unusual evolutionary history including horizontal transmission, degeneration, and domestication into the mating-type switching locus HO. We investigate here the effects of these features on its molecular evolution. In addition, ...

Evolution of divergent DNA recognition specificities in VDE homing endonucleases from two yeast species

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Posey, KLK, V.; Burt, A.; Gimble, F. S.,  Nucleic Acids Research,  32:3947-3956. 2004.
Homing endonuclease genes (HEGs) are mobile DNA elements that are thought to confer no benefit to their host. They encode site-specific DNA endonucleases that perpetuate the element within a species population by homing and disseminate it between species by horizontal transfer. ...

Homing endonuclease genes: the rise and fall and rise again of a selfish element

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Burt, AK, V.,  Current Opinion in Genetics & Development,  14:609-615. 2004.
Homing endonuclease genes (HEGs) are selfish genetic elements that spread by first cleaving chromosomes that do not contain them and then getting copied across to the broken chromosome as a byproduct of the repair process. The success of this strategy will depend on the ...

Site-specific selfish genes as tools for the control and genetic engineering of natural populations

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Burt, A,  Proceedings of the Royal Society B-Biological Sciences,  270:921-928. 2003.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can ...

Adaptation for horizontal transfer in a homing endonuclease

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Koufopanou, VG, M. R.; Burt, A.,  Molecular Biology and Evolution,  19:239-246. 2002.
Selfish genes of no function other than self-propagation are susceptible to degeneration if they become fixed in a population. and regular transfer to new species may be the only means for their long-term persistence. To test this idea we surveyed 24 species of yeast for VDE, a ...

Outcrossed sex allows a selfish gene to invade yeast populations

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Goddard, MRG, D.; Burt, A.,  Proceedings of the Royal Society B-Biological Sciences,  268:2537-2542. 2001.
Homing endonuclease genes (HEGs) in eukaryotes are optional genes that have no obvious effect on host phenotype except for causing chromosomes not containing a cop), of the gene to be cut, thus causing them to be inherited at a greater than Mendelian rate via gene conversion. ...

Recurrent invasion and extinction of a selfish gene

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Goddard, MRB, A.,  Proceedings of the National Academy of Sciences of the United States of America,  96:13880-13885. 1999.
Homing endonuclease genes show super-Mendelian inheritance, which allows them to spread in populations even when they are of no benefit to the host organism. To test the idea that regular horizontal transmission is necessary for the long-term persistence of these genes, we ...

Genetics-driving genes and chromosomes

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Charlesworth, B,  Nature,  332:394-395. 1988.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew ...