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...
Main Authors: | , , , , |
---|---|
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 |
_version_ | 1818615429739839488 |
---|---|
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. |
first_indexed | 2024-12-16T16:33:46Z |
format | Article |
id | doaj.art-d70de93169fb40c885c1f0f4d3b57d23 |
institution | Directory Open Access Journal |
issn | 2001-0370 |
language | English |
last_indexed | 2024-12-16T16:33:46Z |
publishDate | 2016-01-01 |
publisher | Elsevier |
record_format | Article |
series | Computational and Structural Biotechnology Journal |
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 |
work_keys_str_mv | AT silviazucchelli engineeringtranslationinmammaliancellfactoriestoincreaseproteinyieldtheunexpecteduseoflongnoncodingsineuprnas AT laurapatrucco engineeringtranslationinmammaliancellfactoriestoincreaseproteinyieldtheunexpecteduseoflongnoncodingsineuprnas AT francescapersichetti engineeringtranslationinmammaliancellfactoriestoincreaseproteinyieldtheunexpecteduseoflongnoncodingsineuprnas AT stefanogustincich engineeringtranslationinmammaliancellfactoriestoincreaseproteinyieldtheunexpecteduseoflongnoncodingsineuprnas AT diegocotella engineeringtranslationinmammaliancellfactoriestoincreaseproteinyieldtheunexpecteduseoflongnoncodingsineuprnas |