ArticleThe Journal of biological chemistry
HMEJ-based safe-harbor genome editing enables efficient generation of cattle with increased resistance to tuberculosis.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 40 citations in OpenAlex.
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Preventive Immunology for Livestock and Zoonotic Infectious Diseases in the One Health Era: From Mechanistic Insights to Innovative Interventions.Veterinary sciences · 2025Review
- Contributions of large and agricultural animal models to immunology.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety.Functional & integrative genomics · 2025Article
- The 2SP Site Mutation in the Bovine Natural Resistance-Associated Macrophage 1 Promoter Exhibits Antituberculosis Potential.International journal of molecular sciences · 2025Article
- Application of Genomic Selection in Beef Cattle Disease Prevention.Animals : an open access journal from MDPI · 2025Review
- Generation of Anti-Mastitis Gene-Edited Dairy Goats with Enhancing Lysozyme Expression by Inflammatory Regulatory Sequence using ISDra2-TnpB System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CRISPR-mediated editing of β-lactoglobulin (BLG) gene in buffalo.Scientific reports · 2024Article
- Comparison of Multiple Strategies for Precision Transgene Knock-In inInternational journal of molecular sciences · 2023Article
- Modern Approaches to Mouse Genome Editing Using the CRISPR-Cas Toolbox and Their Applications in Functional Genomics and Translational Research.Advances in experimental medicine and biology · 2023Review
- Correction ofFrontiers in genetics · 2023Article
- Application of Gene Editing Technology in Resistance Breeding of Livestock.Life (Basel, Switzerland) · 2022Review
- CRISPR/Cas9-mediated knock-in strategy at the Rosa26 locus in cattle fetal fibroblasts.PloS one · 2022Article
- CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes.Nature communications · 2021Article
- Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype.Frontiers in veterinary science · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CRISPR/Cas9 system has been used in a wide range of applications in the production of gene-edited animals and plants. Most efforts to insert genes have relied on homology-directed repair (HDR)-mediated integration, but this strategy remains inefficient for the production of gene-edited livestock, especially monotocous species such as cattle. Although efforts have been made to improve HDR efficiency, other strategies have also been proposed to circumvent these challenges. Here we demonstrate that a homology-mediated end-joining (HMEJ)-based method can be used to create gene-edited cattle that displays precise integration of a functional gene at the ROSA26 locus. We found that the HMEJ-based method increased the knock-in efficiency of reporter genes by eightfold relative to the traditional HDR-based method in bovine fetal fibroblasts. Moreover, we identified the bovine homology of the mouse Rosa26 locus that is an accepted genomic safe harbor and produced three live-born gene-edited cattle with higher rates of pregnancy and birth, compared with previous work. These gene-edited cattle exhibited predictable expression of the functional gene natural resistance-associated macrophage protein-1 (NRAMP1), a metal ion transporter that should and, in our experiments does, increase resistance to bovine tuberculosis, one of the most detrimental zoonotic diseases. This research contributes to the establishment of a safe and efficient genome editing system and provides insights for gene-edited animal breeding.
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