Germline excision of transgenes in Aedes aegypti by homing endonucleases

被引:25
作者
Aryan, Azadeh
Anderson, Michelle A. E.
Myles, Kevin M.
Adelman, Zach N. [1 ]
机构
[1] Virginia Tech, Fralin Life Sci Inst, Blacksburg, VA 24061 USA
来源
SCIENTIFIC REPORTS | 2013年 / 3卷
关键词
YELLOW-FEVER MOSQUITO; DIRECTED EVOLUTION; ANOPHELES-GAMBIAE; DNA BREAKS; GENE; RECOMBINATION; DROSOPHILA; DERIVATIVES; POPULATION; SEQUENCES;
D O I
10.1038/srep01603
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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, I-CreI and I-SceI are all capable of catalyzing the excision of genomic segments from the Ae. aegypti genome in a heritable manner. Y2-I-AniI demonstrated the highest efficiency at two independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals producing offspring that had lost the target transgene. HE-induced DSBs were found to be repaired via the single-strand annealing (SSA) and non-homologous end-joining (NHEJ) pathways in a manner dependent on the availability of direct repeat sequences in the transgene. These results support the development of HE-based gene editing and gene drive strategies in Ae. aegypti, and confirm the utility of HEs in the manipulation and modification of transgenes in this important vector.
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页数:8
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