Keywords: homing endonuceases

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

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

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

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 ...
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Strategies for Achieving Gene Drive – Over-Replication

GeneConvene Global Collaborative,  GeneConvene Global Collaborative,  2020.
This short video explains how there are essentially three genetic strategies for achieve 'drive' or 'gene drive'.  This video focuses on Over-Replication, a very common strategy associated wtih different types of genetic elements found in nature that 'drive'.  This strategy is ...
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Assessment of a Split Homing Based Gene Drive for Efficient Knockout of Multiple Genes

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

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

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 ...
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Gene drive to reduce malaria transmission in sub-Saharan Africa

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

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) ...
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Gene drive: Evolved and synthetic

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

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 ...
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CRISPR-Cas9: Safeguarding Gene Drives

Harvard University,  ,  2015.
In this animation, learn how effective safeguarding mechanisms developed at the Wyss Institute and Harvard Medical School can be applied to ensure gene drive research is done responsibly in the laboratory. These safeguards enable responsible scientific investigation into how gene ...
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Modelling the spatial spread of a homing endonuclease gene in a mosquito population

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

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

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 ...
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