2025-10-22 エディンバラ大学
<関連情報>
- https://www.ed.ac.uk/news/gene-edited-pigs-resistant-to-deadly-viral-disease
- https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(25)00365-8
DNAJC14遺伝子編集豚は古典的なペスティウイルスに耐性がある DNAJC14 gene-edited pigs are resistant to classical pestiviruses
Helen Crooke ∙ Stefanie Schwindt ∙ Sarah L. Fletcher ∙ … ∙ C. Bruce A. Whitelaw ∙ Norbert Tautz ∙ Simon G. Lillico
Trends in Biotechnology Published:October 22, 2025
DOI:https://doi.org/10.1016/j.tibtech.2025.09.008
Graphical abstract
Technology readiness
We demonstrate that pigs with altered DNAJC14 are resistant to infection with classical swine fever virus under laboratory conditions, placing this discovery at a Technology Readiness Level of 4. While no obvious phenotypic deficits were observed, further work is required to confirm that important welfare and production parameters have not been altered, before commercialization. The closest related prior example is editing of CD163 in pigs to produce animals that are resistant to porcine reproductive and respiratory syndrome virus (PRRSV), another major pathogen. Thus far, gene-edited pigs with PRRSV resistance have been approved in Colombia, Brazil, Dominican Republic, and, most recently, the USA. This reflects maturing regulatory pathways for such products in many jurisdictions. The pigs presented in the current work will provide a valuable additional example to aid regulatory discourse.
Highlights
Pestiviruses incur significant economic and welfare burdens on global livestock production. We used gene editing to produce pigs that were fully resistant to the pestivirus classical swine fever virus.
DNAJC14 is essential for replication of classical pestiviruses in cell lines in vitro, but its importance for these viruses in the context of an animal was unknown.
We used CRISPR/Cas to edit pig DNAJC14 in zygotes, which developed to produce healthy animals.
Primary cells isolated from DNAJC14-edited pigs were resistant to infection with two different pestiviruses: classical swine fever virus and bovine viral diarrhoea virus.
No signs of infection were detected when young adult pigs with edited DNAJC14 were inoculated with classical swine fever virus, demonstrating gene editing as a viable option for control of these devastating pathogens.
Abstract
Infectious diseases remain a major impediment to livestock production, negatively impacting both productivity and welfare. Where key interactions between viruses and host proteins have been identified, it is possible to rationally devise intervention strategies. In vitro studies have identified the host protein DNAJC14 as a core component of the replicative cycle of classical pestiviruses. Outbreaks caused by this group of viruses cause enormous losses in stock farming due to culling and export restrictions. Using CRISPR/Cas9 gene editing, we produced a cohort of pigs with altered DNAJC14. Primary cells from these animals did not support replication of either classical swine fever virus (CSFV) or bovine viral diarrhoea virus (BVDV) in vitro. In vivo challenge with CSFV revealed that the edited pigs displayed complete resistance to infection. This establishes gene editing as an additional strategy that can contribute to the control of classical pestiviruses.
