The translation of novel discoveries from basic research to clinical application is a long, often inefficient, and thus costly process. Accordingly, the process of drug development requires optimization both for economic and for ethical reasons, in order to provide patients with appropriate treatments in a reasonable time frame. Consequently, "Translational Medicine" became a top priority in national and international roadmaps of human health research. Appropriate animal models for the evaluation of efficacy and safety of new drugs or therapeutic concepts are critical for the success of translational research. In this context rodent models are most widely used. At present, transgenic pigs are increasingly being established as large animal models for selected human diseases. The first pig whole genome sequence and many other genomic resources will be available in the near future. Importantly, efficient and precise techniques for the genetic modification of pigs have been established, facilitating the generation of tailored disease models. This article provides an overview of the current techniques for genetic modification of pigs and the transgenic pig models established for neurodegenerative diseases, cardiovascular diseases, cystic fibrosis, and diabetes mellitus.
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http://dx.doi.org/10.1007/s00109-010-0610-9 | DOI Listing |
Xenotransplantation
January 2025
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Gene-edited pigs for xenotransplantation usually contain one or more transgenes encoding human complement regulatory proteins (CRPs). Because of species differences, human CRP(s) expressed in gene-edited pigs may have difficulty inhibiting the activation of exogenous rabbit complement added to a complement-dependent cytotoxicity (CDC) assay. The use of human complement instead of rabbit complement in CDC experiments may more accurately reflect the actual regulatory activity of human CRP(s).
View Article and Find Full Text PDFNat Commun
January 2025
Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
Animal models that accurately reflect COVID-19 are vital for understanding mechanisms of disease and advancing development of improved vaccines and therapeutics. Pigs are increasingly recognized as valuable models for human disease due to their genetic, anatomical, physiological, and immunological similarities to humans, and they present a more ethically viable alternative to non-human primates. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model.
View Article and Find Full Text PDFMol Neurodegener
January 2025
Guangdong Key Laboratory of Non-Human Primate Research, Key Laboratory of CNS Regeneration (Ministry of Education), School of Medicine, GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.
Background: HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention.
Methods: The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA.
Sci Rep
January 2025
Laboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
Transpl Int
January 2025
Pôle de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.
Clinical pancreatic islet xenotransplantation will most probably rely on genetically modified pigs as donors. Several lines of transgenic pigs carrying one and more often, multiple modifications already exist. The vast majority of these modifications aim to mitigate the host immune response by suppressing major xeno-antigens, or expressing immunomodulatory molecules that act locally at the graft site.
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