Type

Journal Article

Authors

Niall Barron
Martin Clynes
Donal O'Gorman
Paula Meleady
Nga T Lao
Michael Henry
Shane Kelly
Clair Gallagher
Laura Breen
Paul S. Kelly

Subjects

Biochemistry

Topics
cho cells oxidative phosphorylation electron transport mitochondrial activity cell growth novel targets productivity growth mammalian cells

Re-programming CHO cell metabolism using miR-23 tips the balance towards a highly productive phenotype. (2015)

Abstract microRNA engineering of CHO cells has already proved successful in enhancing various industrially relevant phenotypes and producing various recombinant products. A single miRNA's ability to interact with multiple mRNA targets allows their regulatory capacity to extend to processes such as cellular metabolism. Various metabolic states have previously been associated with particular CHO cell phenotypes such as glycolytic or oxidative metabolism accommodating growth and productivity, respectively. miR-23 has previously been demonstrated to play a role in glutamate metabolism resulting in enhanced oxidative phosphorylation through the TCA cycle. Re-programming cellular bioenergetics through miR-23 could tip the balance, forcing mammalian production cells to be more productive by favoring metabolic channelling into oxidative metabolism. CHO clones depleted of miR-23 using a miR-sponge decoy demonstrated an average ∼three-fold enhanced specific productivity with no impact on cell growth. Using a cell respirometer, mitochondrial activity was found to be enhanced by ∼30% at Complex I and II of the electron transport system. Additionally, label-free proteomic analysis uncovered various potential novel targets of miR-23 including LE1 and IDH1, both implicated in oxidative metabolism and mitochondrial activity. These results demonstrate miRNA-based engineering as a route to re-programming cellular metabolism resulting in increased productivity, without affecting growth.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Niall Barron, Martin Clynes, Donal O'Gorman, Paula Meleady, Nga T Lao, Michael Henry, Shane Kelly, Clair Gallagher, Laura Breen, Paul S. Kelly

Experts in our system

1
Niall Barron
Dublin City University
Total Publications: 44
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
Donal J O'Gorman
Dublin City University
Total Publications: 42
 
4
Paula Meleady
Dublin City University
Total Publications: 95
 
5
Nga T Lao
Dublin City University
Total Publications: 7
 
6
Michael Henry
Dublin City University
Total Publications: 78
 
7
Shane Kelly
Dublin City University
Total Publications: 6
 
8
Clair Gallagher
Dublin City University
Total Publications: 12
 
9
Laura Breen
Dublin City University
Total Publications: 11
 
10
Paul S. Kelly
Dublin City University
Total Publications: 11