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Development of synthetic selfish elements based on modular nucleases in Drosophila melanogaster.

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Simoni, Alekos 
Siniscalchi, Carla 
Chan, Yuk-Sang 
Huen, David S 
Russell, Steven 


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.



Animals, DNA, DNA End-Joining Repair, Drosophila melanogaster, Endodeoxyribonucleases, Female, Homologous Recombination, Male, Protein Engineering

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Nucleic Acids Res

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Oxford University Press (OUP)
Bill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (via Imperial College London) (LBEE P58006)
Imperial College London (1221)
Bill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (via Imperial College London) (LBEE P41643)