Improved yield of rhEPO in CHO cells with synthetic 5′ UTR

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Title: Improved yield of rhEPO in CHO cells with synthetic 5′ UTR
Authors: Costello, AlanLao, Nga T.Barron, NiallClynes, Martin
Permanent link: http://hdl.handle.net/10197/11043
Date: 15-Feb-2019
Online since: 2019-08-26T14:27:12Z
Abstract: The impact of local structure on mRNA translation is not well-defined pertaining to the 5′ UTR. Reports suggest structural remodelling of the 5′ UTR can significantly influence mRNA translation both in cis and trans however a new layer of complexity has been applied to this model with the now known reversible post-transcriptional chemical modification of RNA. N6-methyladenosine (m6A) is the most abundant internal base modification in mammalian mRNA. It has been reported that mRNAs harbouring m6A motifs in their 5′ UTR have improved translation efficiency. The present study evaluated the addition of putative m6A motifs to the 5′ UTR of a model recombinant human therapeutic glycoprotein, Erythropoietin (EPO), in a direct comparison with an A to T mutant and a no adenosine control. The m6A construct yielded significantly improved EPO titer in transient batch culture over no adenosine and m6T controls by 2.84 and 2.61-fold respectively. This study highlights that refinement of transgene RNA elements can yield significant improvements to protein titer.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Springer Nature
Journal: Biotechnology Letters
Volume: 41
Issue: 2
Start page: 231
End page: 239
Copyright (published version): 2018 Springer
Keywords: 5 UTRN-6-methyladenosinem(6)ACHOBioprocessingSynthetic biology
DOI: 10.1007/s10529-018-2632-2
Language: en
Status of Item: Peer reviewed
Appears in Collections:Chemical and Bioprocess Engineering Research Collection

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