@article{c823efba7f1e4b99893fcf1682cfb26d,
title = "Creating resistance to avian influenza infection through genome editing of the ANP32 gene family",
abstract = "Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections. Breakthrough IAV virus contained IAV polymerase gene mutations that conferred adaptation to the edited chicken ANP32A. Unexpectedly, this virus also replicated in chicken embryos edited to remove the entire ANP32A gene and instead co-opted alternative ANP32 protein family members, chicken ANP32B and ANP32E. Additional genome editing for removal of ANP32B and ANP32E eliminated all viral growth in chicken cells. Our data illustrate a first proof of concept step to generate IAV-resistant chickens and show that multiple genetic modifications will be required to curtail viral escape.",
keywords = "Animals, Chick Embryo, Chickens/genetics, Gene Editing, Influenza A virus/genetics, Influenza in Birds/genetics, RNA-Dependent RNA Polymerase/genetics",
author = "Alewo Idoko-Akoh and Goldhill, {Daniel H.} and Sheppard, {Carol M.} and Dagmara Bialy and Quantrill, {Jessica L.} and Ksenia Sukhova and Brown, {Jonathan C.} and Samuel Richardson and Ciara Campbell and Lorna Taylor and Adrian Sherman and Salik Nazki and Long, {Jason S.} and Skinner, {Michael A} and Holly Shelton and Helen Sang and Barclay, {Wendy S.} and Mike McGrew",
note = "Funding Information: Acknowledgements include; Klaudia Chrzastek, Jean-Remy Sadeyen, Munir Iqbal, Elizabeth Billington, Mohammed Khalid Zakaria, the Pirbright poultry team for support with animal work. Dominique Meunier, Kris Hogan, Frances Thomson, Norman Russell, the Roslin poultry team in the National Avian Research Facility. We thank Norman Russell (RIP) for the photographs of all the chickens. Funding This research was supported by BBSRC with Cobb-Vantress industrial partner project funding BB/S0007911/1 to H.S., BB/S008292/1 to W.B. and J.L., BB/S006796/1 to M.J.M., A.I.A. and H.M.S. and Wellcome Trust award 205100/Z/16/Z to W.B. This work was also supported by the Institute Strategic Grant Funding from the BBSRC (BB/P0.13732/1 and BB/P013759/1) to Roslin Institute and BBS/E/1/00007038 and BBS/E/1/00007039 to the Pirbright Institute. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Funding Information: Acknowledgements include; Klaudia Chrzastek, Jean-Remy Sadeyen, Munir Iqbal, Elizabeth Billington, Mohammed Khalid Zakaria, the Pirbright poultry team for support with animal work. Dominique Meunier, Kris Hogan, Frances Thomson, Norman Russell, the Roslin poultry team in the National Avian Research Facility. We thank Norman Russell (RIP) for the photographs of all the chickens. Funding This research was supported by BBSRC with Cobb-Vantress industrial partner project funding BB/S0007911/1 to H.S., BB/S008292/1 to W.B. and J.L., BB/S006796/1 to M.J.M., A.I.A. and H.M.S. and Wellcome Trust award 205100/Z/16/Z to W.B. This work was also supported by the Institute Strategic Grant Funding from the BBSRC (BB/P0.13732/1 and BB/P013759/1) to Roslin Institute and BBS/E/1/00007038 and BBS/E/1/00007039 to the Pirbright Institute. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-41476-3",
language = "English",
volume = "14",
pages = "1--15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "945",
}