{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:55:25Z","timestamp":1792176925382,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Advances in process optimization and stable CHO cell line engineering have enabled recombinant monoclonal antibody (mAb) titers above 10\u2009g\/L in fed\u2010batch cultures. Despite these advances, the correlation between mAb nucleotide coding sequence and protein yield is still not fully understood. Initial studies with two IgG1 mAbs showed that Lys codon selection at the heavy chain (HC) C\u2010terminus significantly affected yields in certain sequence contexts, as the titer of mAb1 was unchanged by codon selection, while mAb2 titer dropped four\u2010fold with AAG\n                    <jats:sup>Lys<\/jats:sup>\n                    compared to AAA\n                    <jats:sup>Lys<\/jats:sup>\n                    . To determine the factors contributing to this difference, CHO cell lines expressing the two mAb variants with different HC C\u2010terminal variants were generated. The specific C\u2010terminal codon pair GGT\n                    <jats:sup>Gly<\/jats:sup>\n                    \u2013AAG\n                    <jats:sup>Lys<\/jats:sup>\n                    notably reduced HC mRNA transcript levels and mAb yields in CHO expression studies. Metabolic labeling studies using a modified uracil analog revealed that the decreased HC transcript levels resulted from reduced accumulation of nascent HC mRNA. Furthermore, the C\u2010terminal codon pair GGT\n                    <jats:sup>Gly<\/jats:sup>\n                    \u2013AAG\n                    <jats:sup>Lys<\/jats:sup>\n                    was found to broadly influence the expression of other industrially relevant IgG mAb isotypes, including IgG2 and IgG4. This study establishes a connection between the HC C\u2010terminal nucleotide sequence and mAb expression titer, offering insights for optimizing the expression of Fc\u2010containing molecules.\n                  <\/jats:p>","DOI":"10.1002\/bit.70223","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T17:55:36Z","timestamp":1777744536000},"page":"1891-1901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Heavy Chain C\u2010Terminal Codons on Recombinant Monoclonal Antibody Expression Levels"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-0685","authenticated-orcid":false,"given":"Kenneth R.","family":"Carlson","sequence":"first","affiliation":[{"name":"Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Technology Center Indianapolis Indiana USA"},{"name":"Bioprocess Research and 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