Production of antibodies and antibody fragments containing non-natural amino acids in Escherichia coli
| Autor: | Jacquelyn Blake-Hedges, Dan Groff, Wilson Foo, Jeffrey Hanson, Elenor Castillo, Miao Wen, Diana Cheung, Mary Rose Masikat, Jian Lu, Young Park, Nina Abi Carlos, Hans Usman, Kevin Fong, Abigail Yu, Sihong Zhou, Joyce Kwong, Cuong Tran, Xiaofan Li, Dawei Yuan, Trevor Hallam, Gang Yin |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | mAbs, Vol 16, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 19420862 1942-0870 1942-0862 |
| DOI: | 10.1080/19420862.2024.2316872 |
| Popis: | Therapeutic bioconjugates are emerging as an essential tool to combat human disease. Site-specific conjugation technologies are widely recognized as the optimal approach for producing homogeneous drug products. Non-natural amino acid (nnAA) incorporation allows the introduction of bioconjugation handles at genetically defined locations. Escherichia coli (E. coli) is a facile host for therapeutic nnAA protein synthesis because it can stably replicate plasmids encoding genes for product and nnAA incorporation. Here, we demonstrate that by engineering E. coli to incorporate high levels of nnAAs, it is feasible to produce nnAA-containing antibody fragments and full-length immunoglobulin Gs (IgGs) in the cytoplasm of E. coli. Using high-density fermentation, it was possible to produce both of these types of molecules with site-specifically incorporated nnAAs at titers > 1 g/L. We anticipate this strategy will help simplify the production and manufacture of promising antibody therapeutics. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
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