Bioinformatic-Based Design of Engineering Strategies to Increase CHO Cell Biomass Accumulation Rate

Professor David James, University of Sheffield


University of Sheffield logo“As a result of this BIV, Lonza have directly funded two postdoctoral researchers at Sheffield, Dr Alejandro Fernandez-Martell and Dr Joanne Longster for two years, worth over £450,000.”

Professor David James, University of Sheffield

The Challenge

Chinese Hamster Ovary (CHO) cells are the dominant cell factory utilised for biopharmaceutical production and will remain so for the foreseeable future. This biomanufacturing platform underpins a global market in biopharmaceuticals with annual sales exceeding $100 billion.

Slow cell growth rate is a significant core challenge for CHO based biopharmaceutical manufacturing as it restricts the rate at which new products and processes can be developed. Currently, industry relies upon natural genetic variation and associated trial-and-error screening to identify cells with desirable manufacturing characteristics.

There is now an urgent need to shift from screening-led to design-led engineering technologies; embedding prediction, design and engineering of cell factory function at an earlier stage in biomanufacuring process development.

The Research

Professor David James at the University of Sheffield researches into bioprocessing based on mammalian cell factories.

Lonza is one of the world’s leading and most-trusted suppliers to the pharmaceutical, biotech and specialty ingredients markets. Lonza harnesses science and technology to create products that support safer and healthier living and that enhance the overall quality of life.

Professor James applied for a CBMNet Business Interaction Voucher with Lonza to utilise both engineered cells and large genomic datastreams to design and comparatively evaluate new strategies to engineer nutrient transport in CHO cells to enable faster growth and proliferation of these important cell factories.

The Result

It was determined that given the complexity and inherent variability of cellular control mechanisms in CHO cells that together contribute to the ideal (rapidly proliferating, biomass intensive, stable) production phenotype, successful cell engineering strategies to achieve this objective are unlikely to be based on a small number of genetic alterations.

Complex phenotypic traits such as cell growth will require more sophisticated, coordinated control of the expression of multiple cell regulatory systems simultaneously. This goal, to unlock the biosynthetic capacity of CHO cells, is more likely to be achieved via strategies such as directed cellular evolution using appropriate selective environments that permit cells to themselves achieve coordinated/balanced genome engineering.

In this respect, it would be possible to utilize the inherent genetic instability of CHO cells advantageously, balancing genetic instability against evolutionary gain.

The Future

As a result of this BIV, Lonza have directly funded two postdoctoral researchers at Sheffield, Dr Alejandro Fernandez-Martell and Dr Joanne Lonsgter for two years, worth over £450,000.

The Lonza-Sheffield team aim to  combine detailed bioinformatic analysis and high-throughout cell culture technology to develop next generation CHO cell factories that Lonza can employ to intensify biopharmaceutical biomanufacturing processes.