Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Editing livestock genomes with site-specific nucleases

Daniel F. Carlson A E , Wenfang Tan B D , Perry B. Hackett A B C and Scott C. Fahrenkrug A B D
+ Author Affiliations
- Author Affiliations

A Recombinetics Inc., St. Paul, MN 55104, USA.

B The Center for Genome Engineering, University of Minnesota, 1246 University Ave W; Suite 301, Minneapolis, MN 55455, USA.

C Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church St. SE Minneapolis, MN 55455, USA.

D Department of Animal Science, University of Minnesota, 305 Haecker Hall; 1346 Eckles Ave, St. Paul, MN 55108, USA.

E Corresponding author. Email: dan@recombinetics.com

Reproduction, Fertility and Development 26(1) 74-82 https://doi.org/10.1071/RD13260
Published: 5 December 2013

Abstract

Over the past 5 years there has been a major transformation in our ability to precisely manipulate the genomes of animals. Efficiencies of introducing precise genetic alterations in large animal genomes have improved 100 000-fold due to a succession of site-specific nucleases that introduce double-strand DNA breaks with a specificity of 10–9. Herein we describe our applications of site-specific nucleases, especially transcription activator-like effector nucleases, to engineer specific alterations in the genomes of pigs and cows. We can introduce variable changes mediated by non-homologous end joining of DNA breaks to inactive genes. Alternatively, using homology-directed repair, we have introduced specific changes that support either precise alterations in a gene’s encoded polypeptide, elimination of the gene or replacement by another unrelated DNA sequence. Depending on the gene and the mutation, we can achieve 10%–50% effective rates of precise mutations. Applications of the new precision genetics are extensive. Livestock now can be engineered with selected phenotypes that will augment their value and adaption to variable ecosystems. In addition, animals can be engineered to specifically mimic human diseases and disorders, which will accelerate the production of reliable drugs and devices. Moreover, animals can be engineered to become better providers of biomaterials used in the medical treatment of diseases and disorders.

Additional keywords: clustered regularly interspaced short palindromic repeats/Cas9, homology-directed repair, non-homologous end joining, somatic cell nuclear transfer, transcription activator-like effector nucleases, zinc finger nucleases.


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