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

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.

Automated summary

Over the past decades, virus-like particle (VLP)-based gene therapy (GT) has shown promise in treating inherited diseases or cancer. However, the high costs due to inefficient production processes remain a major challenge. This review aims to integrate genome-scale metabolic models (GSMMs) with cell lines used for VLP synthesis, summarizing recent advances and challenges in GSMMs for Chinese hamster ovary (CHO) cells and providing an overview of potential cell lines for GT. Although GSMMs have improved growth rates and recombinant protein production in CHO cells, no GSMM has been established for VLP production. To address this, an overview of existing omics data and the highest reported production titers is provided.