{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:27:56Z","timestamp":1787696876597,"version":"build-2784847793"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["LONG19F5-CI"],"award-info":[{"award-number":["LONG19F5-CI"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["LONG21R3"],"award-info":[{"award-number":["LONG21R3"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cystic fibrosis (CF) is caused by homozygous mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in multi-organ dysfunction and decreased lifespan and quality of life. A durable cure for CF will likely require a gene therapy approach to correct CFTR. Rapid advancements in genome editing technologies, including CRISPR\/Cas9, have already resulted in Food and Drug Administration (FDA) approval for cell-based gene editing therapies, providing new therapeutic avenues for many rare diseases. However, immune responses to gene therapy delivery vectors and editing tools remain a challenge, especially for strategies targeting complex in vivo tissues such as the lung. Previous findings in non-CF healthy individuals reported pre-existing antibody and T cell responses to recombinant Cas9 proteins, suggesting potential additional obstacles for incorporation of clustered regularly interspaced short palindromic repeats (CRISPR)\/Cas9 technologies in gene therapies. To determine whether pre-existing immunity to Cas9 from S. aureus or S. pyogenes was present or augmented in people with CF, anti-Cas9 IgG levels and Cas9-specific T cell responses were determined from peripheral blood samples of people with CF and non-CF healthy controls. Overall, non-CF control and CF samples displayed evidence of pre-existing antibody and T cell responses to both S. aureus and S. pyogenes Cas9, although there were no significant differences between these populations. However, we observed global changes in CF activation of Th1 and CD8 T cell responses as measured by interferon \u03b3 (IFN-\u03b3) and tumor necrosis factor (TNF) that warrant further investigation and mechanistic understanding as this finding has implications not only for CRISPR\/Cas9 gene therapy for people with CF but also for protection against infectious disease.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf041","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T22:56:21Z","timestamp":1758322581000},"source":"Crossref","is-referenced-by-count":3,"title":["Detection of pre-existing immunity to bacterial Cas9 proteins in people with cystic fibrosis"],"prefix":"10.1093","volume":"9","author":[{"given":"Gregory","family":"Serpa","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]},{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoke","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithu","family":"De","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav S J B","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]},{"name":"Department of Pediatrics, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]},{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]},{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6398-3492","authenticated-orcid":false,"given":"Emily A","family":"Hemann","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]},{"name":"Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University Wexner Medical Center , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"2025091918561648400_vlaf041-B1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ymthe.2021.01.010","article-title":"Gene therapy for cystic fibrosis: lessons learned and paths forward","volume":"29","author":"Choi","year":"2021","journal-title":"Mol Ther"},{"key":"2025091918561648400_vlaf041-B2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41467-023-36244-2","article-title":"Future therapies for cystic fibrosis","volume":"14","author":"Allen","year":"2023","journal-title":"Nat Commun"},{"key":"2025091918561648400_vlaf041-B3","doi-asserted-by":"crossref","first-page":"17092","DOI":"10.1038\/nmicrobiol.2017.92","article-title":"A decade of discovery: CRISPR 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