Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs

Mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibo...

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Main Authors: Silvia Zucchelli, Laura Patrucco, Francesca Persichetti, Stefano Gustincich, Diego Cotella
Format: Article
Language:English
Published: Elsevier 2016-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037016300496
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author Silvia Zucchelli
Laura Patrucco
Francesca Persichetti
Stefano Gustincich
Diego Cotella
author_facet Silvia Zucchelli
Laura Patrucco
Francesca Persichetti
Stefano Gustincich
Diego Cotella
author_sort Silvia Zucchelli
collection DOAJ
description Mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation. Among well-established techniques (codon optimization and improvement of mRNA secondary structure), we describe SINEUPs, a family of antisense long non-coding RNAs that are able to increase translation of partially overlapping protein-coding mRNAs. By exploiting their modular structure, SINEUP molecules can be designed to target virtually any mRNA of interest, and thus to increase the production of secreted proteins. Thus, synthetic SINEUPs represent a new versatile tool to improve the production of secreted proteins in biomanufacturing processes.
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spelling doaj.art-d70de93169fb40c885c1f0f4d3b57d232022-12-21T22:24:32ZengElsevierComputational and Structural Biotechnology Journal2001-03702016-01-0114C40441010.1016/j.csbj.2016.10.004Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAsSilvia Zucchelli0Laura Patrucco1Francesca Persichetti2Stefano Gustincich3Diego Cotella4Department of Health Sciences, Università del Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, Università del Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, Università del Piemonte Orientale, Novara, ItalyArea of Neuroscience, SISSA, Trieste, ItalyDepartment of Health Sciences, Università del Piemonte Orientale, Novara, ItalyMammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation. Among well-established techniques (codon optimization and improvement of mRNA secondary structure), we describe SINEUPs, a family of antisense long non-coding RNAs that are able to increase translation of partially overlapping protein-coding mRNAs. By exploiting their modular structure, SINEUP molecules can be designed to target virtually any mRNA of interest, and thus to increase the production of secreted proteins. Thus, synthetic SINEUPs represent a new versatile tool to improve the production of secreted proteins in biomanufacturing processes.http://www.sciencedirect.com/science/article/pii/S2001037016300496Cell factoryRecombinant proteinProtein translationSignal peptidelncRNASINEUP
spellingShingle Silvia Zucchelli
Laura Patrucco
Francesca Persichetti
Stefano Gustincich
Diego Cotella
Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
Computational and Structural Biotechnology Journal
Cell factory
Recombinant protein
Protein translation
Signal peptide
lncRNA
SINEUP
title Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
title_full Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
title_fullStr Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
title_full_unstemmed Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
title_short Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs
title_sort engineering translation in mammalian cell factories to increase protein yield the unexpected use of long non coding sineup rnas
topic Cell factory
Recombinant protein
Protein translation
Signal peptide
lncRNA
SINEUP
url http://www.sciencedirect.com/science/article/pii/S2001037016300496
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