Evidence map›Paper›PMID 37487508›Full record

ArticleACS synthetic biology2023

Protein-Specific Signal Peptides for Mammalian Vector Engineering.

Pamela O'Neill, Rajesh K Mistry, Adam J Brown, David C James

Open access · hybridAbstract read
In one paragraph

Article in ACS synthetic biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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

20 citing papers in PubMed, 31 citations in OpenAlex.

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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

4 authors at 3 institutions in 3 countries.

Pamela O'NeillDepartment of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, U.K.ORCID 0009-0009-4453-2635
Rajesh K MistryAstraZeneca, BioPharmaceutical Development, Cell Culture and Fermentation Sciences, Aaron Klugg Building, Granta Park, Cambridge CB21 6GH, U.K.
Adam J BrownDepartment of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, U.K.
David C JamesDepartment of Chemical and Biological Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, U.K.
Synopsys (Switzerland) · CHAstraZeneca (Poland) · PLUniversity of Sheffield · GB

Funding

Biotechnology and Biological Sciences Research Council
6 · The paper itself

Abstract

Expression of recombinant proteins in mammalian cell factories relies on synthetic assemblies of genetic parts to optimally control flux through the product biosynthetic pathway. In comparison to other genetic part-types, there is a relative paucity of characterized signal peptide components, particularly for mammalian cell contexts. In this study, we describe a toolkit of signal peptide elements, created using bioinformatics-led and synthetic design approaches, that can be utilized to enhance production of biopharmaceutical proteins in Chinese hamster ovary cell factories. We demonstrate, for the first time in a mammalian cell context, that machine learning can be used to predict how discrete signal peptide elements will perform when utilized to drive endoplasmic reticulum (ER) translocation of specific single chain protein products. For more complex molecular formats, such as multichain monoclonal antibodies, we describe how a combination of in silico and targeted design rule-based in vitro testing can be employed to rapidly identify product-specific signal peptide solutions from minimal screening spaces. The utility of this technology is validated by deriving vector designs that increase product titers ≥1.8×, compared to standard industry systems, for a range of products, including a difficult-to-express monoclonal antibody. The availability of a vastly expanded toolbox of characterized signal peptide parts, combined with streamlined in silico/in vitro testing processes, will permit efficient expression vector re-design to maximize titers of both simple and complex protein products.

Indexed as

Antibodies, MonoclonalProtein Sorting SignalsAnimalsCHO CellsCricetinaeCricetulusRecombinant ProteinsAntibodies, MonoclonalProtein Sorting SignalsRecombinant Proteinsmammalianrecombinant proteinsignal peptidetranslocation

Identifiers

PMID37487508
PMCPMC10443038
OpenAlexW4385189443

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.