Abstract
Global population will increase to over nine billion by 2050 with the doubling in demand for meat and milk. To overcome this challenge, it is necessary to breed highly efficient and productive livestock. Furthermore, livestock are also excellent models for human diseases and ideal bioreactors to produce pharmaceutical proteins. Thus, genetic engineering of domestic animals presents a critical and valuable tool to address these agricultural and biomedical applications. Overall, genetic engineering has evolved through three stages in history: transgenesis, gene targeting, and gene editing. Since the birth of the first transgenic pig, genetic engineering in livestock has been advancing slowly due to inherent technical limitations. A major breakthrough has been the advent of somatic cell nuclear transfer, which, for the first time, provided the technical ability to produce site-specific genome-modified domestic animals. However, the low efficiency of gene targeting events in somatic cells prohibits its wide use in agricultural and biomedical applications. Recently, rapid progress in tools and methods of genome engineering has been made, allowing genetic editing from mutation of a single base pair to the deletion of entire chromosomes. Here, we review the major advances of genetic engineer- ing in domestic animals with emphasis placed on the introduction of latest designer nucleases.
Highlights
There is an old Chinese saying: food is the paramount necessity of the people indicating the importance of food security
Emphasis is placed on the recent introduction and applications of designer nucleases, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR-Cas9 in livestock
With approximately 15% of microinjected livestock embryos resulting in live offspring, and a success rate of less than 1% of those embryos resulting in transgenic offspring, embryo survival and transgene integration have been major hurdles in the advancement of transgenic animal production[26]
Summary
There is an old Chinese saying: food is the paramount necessity of the people (in other words, hunger breeds discontentment) indicating the importance of food security. To fulfill the demand for agricultural and biomedical applications as well as fundamental research in animal genetics, extensive efforts have been made to advance the genome modification technologies in livestock (Fig. 2). Thanks to the birth of the cloned sheep, Dolly, gene targeted animals could be produced by performing site-specific genome modification in somatic cells followed by nuclear transfer[14]. This strategy is technically challenging, preventing its wide use in functional characterization of livestock genomes. Emphasis is placed on the recent introduction and applications of designer nucleases, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR-Cas in livestock
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