Biologics Development: Role of UCOEs

In #biologics development, success depends on vector designing/ engineering as only an unique combination of the elements yields the best results. Productivity loss of stable #CellLines over long time is often attributed to aberrant #DNA #methylation and #hypoacetylation of #HistoneH3 contributing to variegated transgene expression or complete #silencing over time.

Out of all gene regulatory elements like STARs, S/MARs etc., UCOEs (Ubiquitous Chromatin Opening Elements) improved transgene expression to the greater extent, reducing production instability.

Characteristics:

1. UCOEs are located close to a housekeeping gene promoter.

2. have at least a 50% overlap with a #CpGisland.

3. are marked with euchromatic #histone modifications.

4. have a binding site for CTCF, a transcription factor with well organized insulator functions.

Examples:

1. TBP/ PSMB1: human

2. HNRPA2B1/ CBX3 (A2UCOE): human

3. SURF1/ SURF2 UCOEs: human

4. Rps3 UCOE: murine

Uses:

1. Full sequence or truncated core fragment UCOEs can be appended upstream of the promoter to boost #Protein production.

2. They increase production #stability during long term culture.

3. Generates a more #homogeneous population of expressing cells and a greater number of high expressing clones.

#hailtothegoodgenes #biobulletins

More to munch on:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9764128/

• https://link.springer.com/article/10.1007/s10616-021-00503-1

• https://www.sciencedirect.com/science/article/abs/pii/S146532492030102X