A General Introduction to MicroRNAs,Their Investigation and Exploitation in CHO Cell Lines - MicroRNAs as Tools in Biopharmaceutical Production - page 10

As alluded to previously, another addition to the repertoire of RNA-based gene
regulation is the use of artificial transcripts, termed “sponges” or “antagomirs” that
titrate endogenous microRNAs away from their target and make it less likely to bind
and repress it. The first miRNA sponges were isolated in plants but these decoys
systems could have many applications in the field of recombinant protein production
as a tool in quality control. For example, by regulating genes involved in stress
response, (Ebert et al. 2007 ; Ebert and Sharp 2010b ; Ebert and Sharp 2010a ).

1.7 Conclusion and Perspectives

Unravelling the influence of microRNAs on recombinant protein production in CHO
cells is only just beginning. As such, despite the classification of the CHO mi-
croRNA library and the finding of a few miR signatures, at this stage it remains
open to question as to whether microRNA levels are strongly linked to the recom-
binant protein production machinery and if their manipulation can be harnessed
to develop improved CHO host cell lines. The yield of recombinant proteins cur-
rently observed in cultivated CHO cell lines often outperform dedicated secretory
cells that live in the body (Wurm 2004 ). These yields reflect rapid advances in
the culturing environment, expression vectors, host cell line development and bio-
engineering over the past 1-2 decades. As researchers begin to understand the biology
of microRNA and the control these exert over gene expression new RNA-based ap-
proaches are being explored to potentially engineer hosts with further improved
phenotypes. However, the diverse number of targets that microRNAs influence and
the fact that miR levels change across culture means that manipulation of microR-
NAs to reliably influence improved phenotypes (e.g. growth, recombinant protein
synthesis) is likely to be challenging and will only become a reality once a bet-
ter appreciation of the biology and targets of miRs in the CHO cell is more fully
developed.

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