Disease occurrence adversely affects livestock production and animal welfare, and have an impact on both human health and public perception of food-animals production. Combined efforts from farmers, animal scientists, and veterinarians have been continuing to explore the effective disease control approaches for the production of safe animal-originated food. Implementing the immunogenomics, along with genome editing technology, has been considering as the key approach for safe food-animal production through the improvement of the host genetic resistance. Next-generation sequencing, as a cutting-edge technique, enables the production of high throughput transcriptomic and genomic profiles resulted from host-pathogen interactions. Immunogenomics combine the transcriptomic and genomic data that links to host resistance to disease, and predict the potential candidate genes and their genomic locations. Genome editing, which involves insertion, deletion, or modification of one or more genes in the DNA sequence, is advancing rapidly and may be poised to become a commercial reality faster than it has thought. The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) [CRISPR/Cas9] system has recently emerged as a powerful tool for genome editing in agricultural food production including livestock disease management. CRISPR/Cas9 mediated insertion of gene for producing tuberculosis resistant cattle, and deletion of gene for producing porcine reproductive and respiratory syndrome (PRRS) resistant pigs are two groundbreaking applications of genome editing in livestock. In this review, we have highlighted the technological advances of livestock immunogenomics and the principles and scopes of application of CRISPR/Cas9-mediated targeted genome editing in animal breeding for disease resistance.
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http://dx.doi.org/10.3390/ani10122236 | DOI Listing |
Alzheimers Dement
December 2024
UCSF Weill Institute for Neurosciences, San Francisco, CA, USA.
Background: Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus.
Method: We generated five different genomic excisions at the C9orf72 locus in a patient-derived iPSC line and a WT line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 FTD/ALS in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes.
Alzheimers Dement
December 2024
University of California San Diego, La Jolla, CA, USA.
Background: Our lab has developed a CRISPR-based, gene-editing strategy that targets the extreme C-terminus (C-term) of APP (amyloid precursor protein) - a gene with a central and indisputable role in AD. We have reported previously that APP C-terminus CRISPRs effectively attenuate APP β-cleavage and Alzheimer's pathology in vivo. Here, we present new data demonstrating the feasibility and efficacy of a clinically-viable, "all-in-one" therapeutic vector that has all the components needed for APP C-terminus editing (Cas enzyme / gRNAs / regulatory elements) packaged into a single AAV.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Genome-wide association studies (GWAS) have identified close to one hundred loci associated with Alzheimer's disease (AD) risk. However, for most of these loci we do not understand the underlying mechanism leading to disease. Crispr genome editing in human induced pluripotent stem cells (hiPSCs) provides a model system to study the effects of these genetic variants in a disease relevant cell type.
View Article and Find Full Text PDFCurr Gene Ther
January 2025
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1968917313, Tehran, Iran.
The 5,000 to 8,000 monogenic diseases are inherited disorders leading to mutations in a single gene. These diseases usually appear in childhood and sometimes lead to morbidity or premature death. Although treatments for such diseases exist, gene therapy is considered an effective and targeted method and has been used in clinics for monogenic diseases since 1989.
View Article and Find Full Text PDFDis Model Mech
January 2025
Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.
Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis, necessitating preclinical models for evaluating novel therapies. Large animal models are particularly valuable for assessing locoregional therapies, which are widely employed across HCC stages. This study aimed to develop a large animal HCC model with tailored tumor mutations.
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