Optimizing VLP production in gene therapy: Opportunities and challenges for in silico modeling

Author(s)
Leopold Zehetner, Diana Széliová, Barbara Kraus, Michael Graninger, Jürgen Zanghellini, Juan A. Hernandez Bort
Abstract

Over the past decades, virus-like particle (VLP)-based gene therapy (GT) evolved as a promising approach to cure inherited diseases or cancer. Tremendous costs due to inefficient production processes remain one of the key challenges despite considerable efforts to improve titers. This review aims to link genome-scale metabolic models (GSMMs) to cell lines used for VLP synthesis for the first time. We summarize recent advances and challenges of GSMMs for Chinese hamster ovary (CHO) cells and provide an overview of potential cell lines used in GT. Although GSMMs in CHO cells led to significant improvements in growth rates and recombinant protein (RP)-production, no GSMM has been established for VLP production so far. To facilitate the generation of GSMM for these cell lines we further provide an overview of existing omics data and the highest production titers so far reported.

Organisation(s)
Department of Analytical Chemistry
External organisation(s)
Baxalta Innovations GmbH
Journal
Biotechnology Journal
Volume
18
ISSN
1860-6768
DOI
https://doi.org/10.1002/biot.202200636
Publication date
07-2023
Peer reviewed
Yes
Austrian Fields of Science 2012
304005 Medical biotechnology, 106005 Bioinformatics
Keywords
ASJC Scopus subject areas
Applied Microbiology and Biotechnology, Molecular Medicine
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/optimizing-vlp-production-in-gene-therapy-opportunities-and-challenges-for-in-silico-modeling(81a552aa-60ac-4eff-b4bf-62893693fbec).html