What is it about?
Manufacturing cell lines are the single most important component of every biologics manufacturing process. These cell lines should express the protein drugs or vaccines at high and consistent level. The paper describes a cell line development process, based on Leap-In transposases, that consistently delivers genetically stable high producer cell lines within a short timeframe. We also demonstrate the comparability between the intermediate stable pools and the derivative clones. This allows initiating PD work, formulation development, toxicology material or even Phase 1 clinical drug substance manufacturing using representative cell substrate while clone generation is still in progress.
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Why is it important?
The main advantages of the system are: - multiple, but always single copy integration sites into transcriptionally active open chromatin regions - robust genetic stability - no payload limit. Multi-ORF expression constructs enable to control protein subunit ratios that are consistent between all the recombinant cells and the original stable pools. With other words, every integration site in every recombinant cell within a pool expresses the subunits at the same ratio. It is particularly important for the novel multi-specific protein drug architectures. -as a consequence of clonal homogeneity, the parental stable pools produce highly comparable material enabling early CMC activities, and material generation (tox or even Phase 1) - the development timelines are among the shortest compared to industry standard. The transfected pools recover significantly faster, and screening ~50-100 clones is sufficient to identify high producer stable clones. This is in stark contrast to the industry standard where thousands of clones need to tested and ranked in order to isolate the rare acceptable clones.
Read the Original
This page is a summary of: Accelerating and de‐risking CMC development with transposon‐derived manufacturing cell lines, Biotechnology and Bioengineering, April 2021, Wiley, DOI: 10.1002/bit.27742.
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