Engineering mammalian protein secretion: toward the convergence of high-throughput biology and computational methods
File(s)
Published version
Author(s)
Gabrielli, Jacopo
Lewis, Nathan E
Kontoravdi, Cleo
Ceroni, Francesca
Type
Journal Article
Abstract
Protein secretion in mammalian cells is the active transport of proteins from the cytoplasm to the extracellular space. It plays a fundamental role in mammalian physiology and signaling, as well as biotherapeutics production and cell and gene therapies. The efficacy of protein secretion, however, is impacted by features of the secreted protein itself, and the host-cell machinery that supports each step of the secretion process. High-throughput techniques such as microfluidics, cell display, and cell encapsulation assays for the study and engineering of secreted proteins are transforming biomedical knowledge and our ability to modulate protein secretion. In addition, computational advances, including signal peptide modeling, whole-protein machine learning models, and genome-scale simulations, are opening new pathways for rational design of protein secretion. Here, we highlight recent developments in secretion engineering that are leading to the convergence of high-throughput experimentation and machine learning methods and can help address current challenges in bioproduction and support future efforts in cell and gene therapy while enabling new modalities.
Date Issued
2025-12-17
Date Acceptance
2025-12-01
Citation
Cell Systems, 2025, 16 (12), pp.101424-101424
ISSN
2405-4712
Publisher
Elsevier BV
Journal / Book Title
Cell Systems
Volume
16
Issue
12
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41412115
PII: S2405-4712(25)00257-1
Subjects
bioproduction
biotherapeutics
cell encapsulation
computational protein design
high throughput
microfluidics
protein engineering
protein secretion
synthetic biology
systems biology
Humans
Computational Biology
Animals
Machine Learning
Protein Engineering
Mammals
Proteins
High-Throughput Screening Assays
Protein Transport
Publication Status
Published
Coverage Spatial
United States
Article Number
101424
Date Publish Online
2025-12-17