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Advances in genetic modification of farm animals using zinc-finger nucleases (ZFN)

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Abstract

Genome editing tools (GET), including zinc-finger nucleases (ZFN), transcription activator-like endonucleases (TALENS), and meganucleases possess long recognition sites and are thus capable of cutting DNA in a very specific manner. These genome editing tools mediate targeted genetic alterations by enhancing DNA mutation frequency via induction of double-strand breaks at a predetermined genomic site. Compared to conventional homologous recombination based gene targeting, GETs can increase gene targeting and gene disruption via mutagenic DNA repair more than 10,000-fold. Recently, a novel class of genome editing tools was described that uses RNAs to target a specific genomic site. The CRISPR/Cas9 system is capable of targeting even multiple genomic sites in one shot and thus could be superior to ZFNs or TALEN. Current results indicate that these tools can be successfully employed in a broad range of organisms which renders them useful for improving the understanding of complex physiological systems, producing transgenic animals, including creating large animal models for human diseases, creating specific cell lines, and plants, and even for treating human genetic diseases. This review provides an update on the use of ZFNs to modify the genome of farm animals, summarizes current knowledge on the underlying mechanism, and discusses new opportunities for generating genetically modified farm animals.

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Abbreviations

CRISPR:

Clustered regularly interspaced short palindromic repeats

DSB:

Double-strand break

EGFP:

Enhanced green fluorescent protein

FACS:

Fluorescence-activated cell sorting

GET:

Genome editing tools

HR:

Homologous recombination

HDR:

Homology-directed repair

IPS:

Induced pluripotent stem cells

NHEJ:

Nonhomologous end joining

SCNT:

Somatic cell nuclear transfer

SSB:

Single-strand break

TALEN:

Transcription activator-like effector endonuclease

ZF:

Zinc-finger

ZFN:

Zinc-finger nuclease

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Author notes

  1. Bjoern Petersen

    Present address: Rebirth, Cluster of Excellence, Hannover Medical School, Hoeltystrasse 10, Mariensee, 31535, Neustadt, Germany

Authors and Affiliations

  1. Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Mariensee, Neustadt a. Rbge, Hoeltystrasse 10, Mariensee, 31535, Neustadt, Germany

    Bjoern Petersen & Heiner Niemann

  2. Rebirth, Cluster of Excellence, Hannover Medical School, Hoeltystrasse 10, Mariensee, 31535, Neustadt, Germany

    Heiner Niemann

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  1. Bjoern Petersen
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  2. Heiner Niemann
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Correspondence to Heiner Niemann.

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Responsible Editors: Natalay Kouprina and Vladimir Larionov

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Petersen, B., Niemann, H. Advances in genetic modification of farm animals using zinc-finger nucleases (ZFN). Chromosome Res 23, 7–15 (2015). https://doi.org/10.1007/s10577-014-9451-7

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