Fast predictive expression platform – CHO-K1 with transposase
May 6-11, 2018
The Mammalian Expression group in Therapeutics Discovery Research produces panels of therapeutic candidates in high-throughput (HT) for early stage screening in addition to generating larger productions that are used for manufacturability assessment, pre-clinical PK, and efficacy studies. As our molecule types expand from monoclonal antibodies to include various bispecific modalities, the ability to predict how a molecule will behave in our stable manufacturing host becomes more difficult. To more quickly predict characteristics and manufacturability of our candidate therapeutics, we are developing in-house stable expression systems. The transposase is a mobile genetic element that efficiently transposes between vectors and chromosomes via a “cut and paste” mechanism. Because the transposase facilitates non-random, efficient genetic integration, we investigated the possible incorporation of this technology into our current in-house transient expression vector system. We have observed that its stable-like integration properties provide us with a foundation for enabling a short production time, comparable with a transient expression system, while generating proteins with attributes that are predictive of our manufacturing system. This approach has been validated and implemented with our CHO-K1 stable expression system. With this technology, we are able to reliably generate the diverse array of therapeutic candidate modalities in a high-throughput format while achieving higher predictability of material derived from our manufacturing hosts.
Bram D. Estes, Eric Gislason, Darren Bates, Jennitte Stevens, and Zhulun Wang, "Fast predictive expression platform – CHO-K1 with transposase" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/ccexvi/4