CRISPR mediated PRRS resistant pigs: biological success, welfare implications, and ethical regulatory challenges for sustainable swine production

Porcine reproductive and respiratory syndrome (PRRS) remains one of the most significant health and welfare challenges in global pig production. The disease is associated with substantial economic losses, impaired herd health, increased antimicrobial use, and ongoing animal welfare concerns. Despite widespread implementation of vaccination, biosecurity, and herd stabilization strategies, PRRS continues to persist endemically in many production systems, highlighting the need for additional disease-control approaches. Recent advances in genome editing have enabled the development of host-directed resistance strategies in pigs. In particular, targeted editing of the scavenger receptor CD163, a key host factor required for PRRS virus entry into macrophages, using CRISPR-Cas9 has demonstrated resistance to several PRRSV strains in experimental models. Deletion of the SRCR5 domain of CD163 prevents viral infection while largely preserving normal receptor function, representing a more targeted approach compared with complete gene knockout. Current evidence suggests resistance to both major PRRSV genotypes, although most data derive from controlled experimental studies rather than commercial field conditions. Important considerations remain regarding long-term health and welfare outcomes, immune competence under production environments, ethical considerations surrounding germline genome editing, and differences in regulatory frameworks that may influence adoption. From a pig health management perspective, genome-edited PRRS resistance should be viewed as a complementary strategy rather than a replacement for established control measures such as vaccination, biosecurity, and herd health management. Careful evaluation, veterinary oversight, and coordinated regulatory guidance will be necessary to determine how this technology may be integrated responsibly into future PRRS control programs.