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

02.05.2023

Leopold Zehetner, Diana Széliová, Barbara Kraus, Michael Graninger, Jürgen Zanghellini, and Juan Antonio Hernández Bort

Published in Biotechnology J. 18, 7. 2023.

doi.org/10.1002/biot.202200636

 

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.

Overview of current strategies for bioprocess optimization and host-virus platforms in gene therapy. Implementing genome-scale metabolic models for these cell lines based on multi-omics data may result in higher titers.