Pioneering Chicken Sterile Surrogate Hosts for Advanced Genome Engineering The Engineering Biology Hub at the Roslin Institute has led transformative innovations in avian genome engineering, culminating in the creation of sterile surrogate host chickens, a breakthrough platform for efficient and ethical genetic modification in poultry. This pioneering system accelerates genetic research and biotechnological applications in agriculture and biomedical science, positioning the Hub at the forefront of gene editing in poultry.Chickens are globally significant in agriculture and research, but their complex embryonic structure has historically hindered efficient genetic modification. Earlier approaches using lentiviral vectors at Roslin enabled transgenesis but were limited by imprecision, low germline transmission rates, and extended timelines, often requiring several generations to establish a stable genetically altered (GA) chicken line. The Innovation: Sterile Surrogate HostsA major leap forward came with the development of sterile surrogate host chickens. These birds are engineered so their natural germline cells can be selectively ablated via a chemical compound during embryonic development. Once endogenous primordial germ cells (PGCs) have been ablated, scientists introduce lab-cultured and gene-edited PGCs, stem cells destined to become sperm or eggs. This innovation offers 100% germline transmission of the modified cells in the first generation, eliminating the need for multiple breeding cycles and reducing both time and animal use.The sterile surrogate host system has enabled rapid development of research models and agricultural lines:Disease-Resistant Breeds: Gene edits introduced to confer resistance to poultry viruses.Immune System Models: Knock-in and knock-out lines for poorly understood avian immune genes.Sex Determination & Eye Development: Novel insights into avian sex determination (via DMRT1) and visual system defects (ocular coloboma).Climate-Resilient Layers: Introduction of feather traits for better adaptation in tropical climates. Chicks hatched from sterile surrogate host hens Engineering Biology in Action: Impact & Future VisionRefined PGC culture now enables efficient transgenesis and precise CRISPR/Cas9 editing, reducing the time to generate a GA chicken line from two years to under 12 months. This approach also supports the 3Rs by significantly reducing the number of animals required.These advances are driving impact and will continue to unlock breakthroughs in:Basic and biomedical researchVaccine developmentSustainable agricultureEfficient regeneration of chickens from cryopreserved PGCs A Collaborative Effort and Advanced InfrastructureThe creation of sterile surrogate host chickens brought together specialists in cell and developmental biology. Research was supported by the dedicated avian PGC culture lab and National Avian Research Facility (NARF) at the Roslin Institute, that provides:Avian PGC Culture and CryopreservationIncubation and HatchingPoultry Holding UnitsAvian Gene Editing and TransgenesisAnimal welfare was a core principle throughout the development of the line. All procedures were conducted to the highest ethical standards, in close collaboration with trained animal technicians and the Named Veterinary Surgeon. Key publications Ballantyne et al. Nature Communications (2021) https://doi.org/10.1038/s41467-020-20812-xHu et al. eLife (2022) https://doi.org/10.7554/eLife.74036Idoko-Akoh et al. Nature Communications (2023) https://doi.org/10.1038/s41467-023-41476-3Wu et al. Frontiers in Immunology (2023) https://doi.org/10.3389/fimmu.2023.1273661Chan et al. Scientific Reports (2025) https://doi.org/10.1038/s41598-025-94589-8Fallahshahroudi et al. Nature (2025) https://doi.org/10.1038/s41586-025-09256-9 Introduction of Primordial Germ Cells into a developing chicken embryo This article was published on 2025-10-21