Genome-edited livestock to secure sustainability

Tad Sonstegard; Jon Bostrom; Kyra Martins; Eui-Soo Kim; Carolina Correia; David MacHugh; Sabreena Larson; Daniel Carlson

doi:10.1071/RD24145

REVIEW (Open Access)

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Genome-edited livestock to secure sustainability

Tad Sonstegard

^A ^* , Jon Bostrom ^A , Kyra Martins ^A , Eui-Soo Kim ^A , Carolina Correia ^B , David MacHugh ^B , Sabreena Larson ^A and Daniel Carlson ^A

+ Author Affiliations

- Author Affiliations

^A Acceligen, Recombinetics, Eagan, MN, USA.

^B UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.

^* Correspondence to: tad@acceligen.com

Reproduction, Fertility and Development 37, RD24145 https://doi.org/10.1071/RD24145

© 2025 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Sustainable improvement of production in most tropical dairy systems is a significant challenge, because the cattle breeds with the most genetic potential for milk output relative to native tropical breeds have not been selected for these types of environments. Multiplex genome editing provides a potential solution to introduce beneficial sequence variants (SVs) into elite animals for tropical adaptation in a single generation. Bovine sequence variants for heat tolerance, stature, milk yield, and disease-tolerance traits were identified and genotyped across indigenous African, dairy Zebu, and dairy Taurine breeds to validate those targets best suited for introgression by genome editing. In vitro fertilized embryos from a series of matings were used to produce embryonic stem cells (ESCs) and were subsequently multiplexed edited prior to cloning by somatic cell nuclear transfer. A set of best target SVs for genome editing was established for the Holstein and Gir breeds. ESCs were produced and cloned following treatment and validation screening for multiplex alterations of up to four target genes. Currently, 12 animals have been born, and all the mature males have produced viable semen that will be submitted for regulatory review in a series of countries in Sub-Saharan Africa and South America. Multiplex genome editing based on homology-directed repair combined with cloning of bovine ESCs provides an opportunity to initiate genetic improvement of polygenic traits in cattle. Combining genomics and genome editing provides new opportunities to breed more resilient dairy animals for the tropics that should improve animal and farmer livelihoods.

Keywords: bovine embryonic stem cells, bovine tuberculosis, cattle, heat stress, homology-directed repair, multiplex genome editing, SNP genotyping, trypanosomiasis.

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