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Engineering mammalian cell factories with SINEUP noncoding RNAs to improve translation of secreted proteins
- Publication Year :
- 2015
-
Abstract
- Whenever the function of a recombinant protein depends on post-translational processing, mammalian cells become an indispensable tool for their production. This is particularly true for biologics and therapeutic monoclonal antibodies (MAbs). Despite some drawbacks, Chinese Hamster Ovary (CHO) cells are the workhorse for MAbs production in academia and industry. Several methodologies have been adopted to improve expression and stability, including methods based on selective pressure or cell engineering. We have previously identified SINEUPs as a new functional class of natural and synthetic long non-coding RNAs that through the activity of an inverted SINEB2 element are able to promote translation of partially overlapping sense coding mRNAs. Here we show that by taking advantage of their modular structure, synthetic SINEUPs can be designed to increase production of secreted proteins. Furthermore, by experimentally validating antisense to elastin (AS-eln) RNA as a natural SINEUP, we show that SINEUP-mediated control may target extracellular proteins. These results lead us to propose synthetic SINEUPs as new versatile tools to optimize production of secreted proteins in manufacturing pipelines and natural SINEUPs as new regulatory RNAs in the secretory pathways.
- Subjects :
- Signal peptide
Cell factory
Luciferase assay
Molecular Sequence Data
Computational biology
CHO Cells
Biology
Cricetulus
Genetic
SINEUP
Settore BIO/13 - Biologia Applicata
Sense (molecular biology)
Protein biosynthesis
Genetics
Animals
Humans
RNA, Antisense
Antisense
Cell Engineering
CHO cell
Secretory Pathway
Protein Biosynthesi
Base Sequence
Animal
Chinese hamster ovary cell
Medicine (all)
RNA
Elastin
Long noncoding RNA
Serum-free
Cell Adhesion Molecules
RNA, Long Noncoding
Recombinant Proteins
Protein Biosynthesis
Translation (biology)
General Medicine
Recombinant Protein
Long non-coding RNA
Cell Adhesion Molecule
Long Noncoding
Cricetulu
Function (biology)
Human
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....bf59e255c94ab2f2e9283bfb71a6cfda