title: Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs.
abstract: 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.
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy; Area of Neuroscience, SISSA, Trieste, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchelli
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Patrucco
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Persichetti
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy; Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
authors.affiliation: Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Cotella
keywords: CHO, Chinese hamster ovary; Cell factory; ER, Endoplasmic reticulum; MAb, monoclonal antibody; Protein translation; Recombinant protein; SINE, short interspersed nuclear element; SINEUP; SME, small and medium-sized enterprise; SP, Signal peptide; Signal peptide; lncRNA; lncRNA, long non-coding RNA