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Heritable gene targeting in zebrafish using customized TALENs

Nature Biotechnology volume 29, pages 699–700 (2011)Cite this article

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To the Editor:

Studies of targeted gene modifications are of great interest in basic research as well as for clinical and agricultural applications1. In the February issue of Nature Biotechnology, two articles reported genomic modifications using transcription activator-like (TAL) effectors2,3. Using fusion proteins, each comprising a TAL effector DNA binding domain and a FokI cleavage domain, Miller et al.2 reported that TAL effector nucleases (TALENs) successfully disrupted target genes in cultured human cells. Zhang et al.3 showed that TAL effectors can be used to regulate endogenous gene transcription. Compared with zinc-finger proteins4,5, TAL effectors permit more predictable and specific binding to target DNA6, and therefore allow researchers to engineer genomes precisely without the need for laborious screening to identify a DNA binding domain with the requisite specificity. TALENs can induce DNA double-stranded breaks (DSBs) in yeast7. Gene targeting using TALENs has also been achieved in nematodes8 and human pluripotent cells9. However, it has not, to our knowledge, yet been demonstrated in a vertebrate organism. Here we report the use of TALENs to disrupt both of the two endogenous zebrafish genes we targeted and show that the mutations are transmitted through the germ line.

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Figure 1: Targeted and heritable disruption of the tnikb gene in zebrafish using TALENs.

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Acknowledgements

The authors thank R. Jiao, W. Wang and X. Tong for helpful discussions; H. Xin, C. Zhang and Z. Jiang for help in the luciferase SSA recombination assay; F. Tang, Y. Zhang and P. Xu at the Biodynamic Optical Imaging Center (BIOPIC) for help in deep sequencing; Y. Gao and J. Zhang for laboratory management and technical support; and Y. Jia, J. Chen and H. Cui for maintenance of zebrafish facility. This work was partially supported by grants from National Natural Science Foundation of China (NSFC) (30730056) and 973 program (2011CBA01000, 2007CB914502).

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Authors and Affiliations

  1. Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing, P.R. China

    Peng Huang, An Xiao, Zuoyan Zhu & Bo Zhang

  2. Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University, Shenzhen Graduate School, Shenzhen University Town, Shenzhen, P.R. China

    Peng Huang & Shuo Lin

  3. College of Plant Protection, Nanjing Agricultural University, Nanjing, P.R. China

    Mingguo Zhou

  4. Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA

    Shuo Lin

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  1. Peng Huang
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Correspondence to Shuo Lin or Bo Zhang.

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The authors declare no competing financial interests.

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Supplementary Figures 1–7, Supplementary Tables 1–3, Supplementary Sequences and Supplementary Methods (PDF 1245 kb)

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Huang, P., Xiao, A., Zhou, M. et al. Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol 29, 699–700 (2011). https://doi.org/10.1038/nbt.1939

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