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Journal of equine veterinary science2016; 41; 1-6; doi: 10.1016/j.jevs.2016.03.008

Genome Editing in Large Animals.

Abstract: Genome editing in large animals has tremendous practical applications, from more accurate models for medical research through improved animal welfare and production efficiency. Although genetic modification in large animals has a 30 year history, until recently technical issues limited its utility. The original methods - pronuclear injection and integrating viruses - were plagued with problems associated with low efficiency, silencing, poor regulation of gene expression, and variability associated with random integration. With the advent of site specific nucleases such as TALEN and CRISPR/Cas9, precision editing became possible. When used on their own, these can be used to truncate or knockout genes through non-homologous end joining (NHEJ) with relatively high efficiency. When used with a template containing desired gene edits, these can be used to allow insertion of any desired changes to the genome through homologous recombination (HR) with substantially lower efficiency. Consideration must be given to the issues of marker sets and off-target effects. Somatic cell nuclear transfer is most commonly used to create animals from gene edited cells, but direct zygote injection and use of spermatogonial stem cells are alternatives under development. In developing gene editing projects, priority must be given to understanding the potential for off-target or unexpected effects of planned edits, which have been common in the past. Because of the increasing technical sophistication with which it can be accomplished, genome editing is poised to revolutionize large animal genetics, but attention must be paid to the underlying biology in order to maximize benefit.
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Publication Date: 2016-03-25 PubMed ID: 27766006PubMed Central: PMC5067081DOI: 10.1016/j.jevs.2016.03.008Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the advancements and challenges in the process of genome editing in larger animals with the aim to increase the accuracy of medical models, enhance animal welfare and improve production efficiency.

Utility and Limitations of Genome Editing in Large Animals

  • Genome editing in large animals has tremendous practical applications. It can create more accurate models for medical research, improve animal welfare, and increase production efficiency.
  • Despite being a practice with a 30-year history, genome editing in large animals has faced significant limitations due to technical issues.
  • Early methods, such as pronuclear injection and integrating viruses, were problematic due to low efficiency, poor regulation of gene expression, and variability linked to random integration.

Advancements in Genome Editing Techniques

  • The advent of site-specific nucleases, such as TALEN and CRISPR/Cas9, has made precision genome editing possible.
  • When used alone, these techniques can effectively truncate or knockout genes through a process called non-homologous end joining (NHEJ).
  • When used with a template containing the desired gene changes, these methods can enable the insertion of changes to the genome through a process called homologous recombination (HR), although at a lower efficiency.

Concerns and Consideration in Genome Editing

  • The article urges readers to take into consideration the issues of marker sets and potential off-target effects.
  • Somatic cell nuclear transfer is the most common method utilized to create animals from gene-edited cells. Alternatives include direct zygote injection and the use of spermatogonial stem cells.
  • During the development of gene editing projects, priority should be given to understanding the potential for off-target or unexpected results of planned edits, a concern that has been prominent in the past.

Future of Genome Editing in Large Animals

  • Given the increasing technical sophistication, genome editing is set to revolutionize large animal genetics. However, to maximize benefits, researchers must pay close attention to the nuances of the underlying biology.

Cite This Article

APA
West J, Gill WW. (2016). Genome Editing in Large Animals. J Equine Vet Sci, 41, 1-6. https://doi.org/10.1016/j.jevs.2016.03.008

Publication

Journal of equine veterinary science
ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Volume: 41
Pages: 1-6

Researcher Affiliations

West, James
  • AgGenetics, Nashville, TN; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Gill, W Warren
  • AgGenetics, Nashville, TN; School of Agribusiness and Agriscience, Middle Tennessee State University, Murfreesboro, TN.

Grant Funding

  • R01 HL095797 / NHLBI NIH HHS

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This article has been cited 11 times.
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