Evidence map›Paper›PMID 30682623›Full record

ArticleiScience2019

Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.

Madhuresh Sumit, Sepideh Dolatshahi, An-Hsiang Adam Chu, Kaffa Cote, John J Scarcelli, Jeffrey K Marshall, Richard J Cornell, Ron Weiss, Douglas A Lauffenburger, Bhanu Chandra Mulukutla and 1 more

Abstract read
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Madhuresh SumitCulture Process Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
Sepideh DolatshahiDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
An-Hsiang Adam ChuAnalytical Research and Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
Kaffa CoteAnalytical Research and Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
John J ScarcelliCell Line Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
Jeffrey K MarshallAnalytical Research and Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
Richard J CornellAnalytical Research and Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Douglas A LauffenburgerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Bhanu Chandra MulukutlaCulture Process Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA. Electronic address: bhanuchandra.mulukutla@pfizer.com.
Bruno FigueroaCulture Process Development, Bio Therapeutics Pharmaceutical Sciences, Pfizer, 1 Burtt Road, Andover, MA 01810, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies. A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately. However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases. Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells. Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period. The steps involving galactose and sialic acid addition were determined as temporal bottlenecks. Our results show that galactose, and not manganese, is able to mitigate the temporal bottleneck, despite both being known effectors of galactosylation. Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.

Indexed as

Industrial BiotechnologyMetabolomicsProcess BiotechnologyTranscriptomics

Identifiers

PMID30682623
PMCPMC6352710

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.