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SSPC Impact Case Study: Health

SSPC Impact Case Study: Biologics

Improving the efficiency of biotherapeutic production

Project Lead:

Dr Paula Meleady, Assistant Professor, School of Biotechnology, Dublin City University

Areas of Impact:

Commercialisation, Health, Training

Scientific Domains:

Biologics / Drug Product, Data Analytics

Proteomic and Post-translational modification characterisation of recombinant Chinese hamster ovary (CHO) cells to improve the efficiency of biotherapeutic production

Paula Meleady’s research is based on the ‘Proteomic and Post-translational modification characterisation of recombinant Chinese hamster ovary (CHO) cells to improve the efficiency of biotherapeutic production.’  In CHO production cell cultures, the expression of high levels of recombinant biopharmaceuticals is linked to inducing endoplasmic reticulum (ER) stress, causing enhanced unfolded protein response (UPR) levels to maintain cell viability and productivity. ER stress mechanisms are poorly understood in CHO cells and are a major bottleneck in improving the efficiency of production of high-cost recombinant biopharmaceuticals.

Ubiquitination targets substrates (e.g., misfolded proteins) for degradation but also has important regulatory control functions including cell cycle regulation, translation, apoptosis, etc. and hence is likely to be central to understanding and controlling productivity of recombinant biotherapeutics. We are investigating the proteome and the ubiquitinated proteome of CHO cell lines expressing industrially relevant biotherapeutics, chosen for different bioprocess phenotypes (e.g., temperature shift, culture longevity) and different levels of productivity, using advanced LC-MS/MS strategies to gain a better understanding of how ubiquitination is involved in the regulation of these phenotypes (Ryan et al. 2023)1. From the work to date we have identified several promising protein targets for cell engineering to improve growth and productivity of recombinant CHO cells.

Paula’s group is currently collaborating with the biopharma industry investigating proteomic strategies to identify process changes that can affect the productivity and product quality of biopharmaceutical products from recombinant CHO Cells.

Ryan D, Sideri C, Efeoglu E, Henry M, Meleady P. Label-free quantitative proteomics analysis of producer and non-producer Chinese Hamsters Ovary (CHO) cells under ER stress conditions. Curr. Res. Biotechnol. 2023, 10014. doi.org/10.1016/j.crbiot.2023.100141

The long-term impact from the work would be to improve the efficiency of biopharmaceutical production from recombinant mammalian cell lines such as CHO cells, with the ultimate aim to drive down costs of expensive recombinant drugs to the patient and healthcare providers. We are also training PhD and postdoctoral scientists for the biopharma industry with skills in mammalian cell culture, protein analytics, proteomics and mass spectrometry.

For full list of publications see https://scholar.google.com/citations?user=Ur9UsgIAAAAJ&hl=en

Selected publications (biopharma-related)

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