Accelerating and de‐risking CMC development with transposon‐derived manufacturing cell lines
| العنوان: | Accelerating and de‐risking CMC development with transposon‐derived manufacturing cell lines |
|---|---|
| المؤلفون: | Varsha Sitaraman, Surya Karunakaran, Jessica Choi, Sowmya Rajendran, Molly Hunter, Jeremy Minshull, Maggie Lee, Rebecca Wang, Nicolay V. Kulikov, Ferenc Boldog, Calvin Tang, Lynn Webster, Divya Vavilala, Sowmya Balasubramanian, Harpreet Kaur |
| المصدر: | Biotechnology and Bioengineering |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0106 biological sciences, 0301 basic medicine, Transposable element, transposon, Concatemer, Genetic stability, Transgene, transposase, cell line development, Transposases, integration, Bioengineering, Computational biology, CHO Cells, Biology, 01 natural sciences, Applied Microbiology and Biotechnology, Article, Cell Line, Engineering Science of Biological Systems, 03 medical and health sciences, chemistry.chemical_compound, ARTICLES, Mice, Cricetulus, 010608 biotechnology, Animals, Humans, Leap‐In transposase, Transgenes, Promoter Regions, Genetic, Transposase, Mammals, Biological Products, Chinese hamster ovary cell, stable pools, Clone Cells, 030104 developmental biology, chemistry, DNA Transposable Elements, Manufacturing cell, Recombination, Biotechnology |
| الوصف: | The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein‐based biologic drugs. Here, we describe the Leap‐In Transposase® platform, a novel transposon‐based mammalian (e.g., Chinese hamster ovary) cell line development system that produces high‐titer stable pools with productivity and product quality attributes that are highly comparable to clones that are subsequently derived therefrom. The productivity distributions of clones are strongly biased toward high producers, and genetic and expression stability is consistently high. By avoiding the poor integration rates, concatemer formation, detrimental transgene recombination, low average expression level, unpredictable product quality, and inconsistent genetic stability characteristic of nonhomologous recombination methods, Leap‐In provides several opportunities to de‐risk programs early and reduce timelines and resources. Assessment of integrated copy numbers by ddPCR and productivity assessments from representative production cultures demonstrate that >90% of the clones established by Leap–In transposons maintain the To productivity and copy number levels |
| اللغة: | English |
| تدمد: | 1097-0290 0006-3592 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c24d082224fb964013c4487cc667cd8d http://europepmc.org/articles/PMC8252637 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c24d082224fb964013c4487cc667cd8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970290 00063592 |
|---|