Already undergoing a revolution in speed and bioengineering capabilities, the discipline of biological expression is beginning to assess options that previously were considered “for research purposes only” as real candidates for bioprocessing. Scientists at the American Type Culture Collection (ATCC) are among several organizations that are engineering cell lines for improved expression of high-titer biologics that fulfill well-defined critical quality attributes (CQAs) for product safety and efficacy. A new industry–academia consortium seeks to bring forth not only viable but superior alternatives to Chinese hamster ovary (CHO) cell expression systems. And other researchers are working to create cell-free production systems that might one day disrupt the entire concept of upstream production. Read the articles in this BPI Featured Report to learn how the biopharmaceutical industry is leveraging emerging and underexplored protein-expression systems to treat myriad conditions. 

Avenues for Innovation: The Latest in Cell-Line Engineering and Development
by Cheryl Scott
Herein, BPI’s senior technical editor reports on discussions of protein-expression systems from the March 2021 BioProcess International US West Conference and Exhibition. Upstream presentations addressed three topics: strategies for ensuring CHO cell-line stability, expression of new modalities and using new hosts, and technologies for speeding along cell-line development programs.

Increasing Expression Titers: New Technologies Could Help Other Cell Lines Catch Up to CHO
by Cheryl Scott, with Fang Tian
Although CHO cells and their derivatives are used most commonly for therapeutic-protein expression, several other mammalian cell lines have been approved for complex-protein production, including baby hamster kidney (BHK21) cells, murine myeloma cell lines (NS0 and Sp2/0), human embryonic kidney (HEK293) cells, and other human cell lines (HT-1080, PER.C6, CAP, and HuH-7). BPI’s senior technical editor spoke with Fang Tian (lead scientist and head of cell biology research and development at ATCC) this past spring to learn about industry efforts to improve expression titers in mammalian-cell systems.

Engineering Alternatives: Modern Technology Enables Expression System Developers to Think Beyond CHO Cells
by Gareth Macdonald and Cheryl Scott, with J. Christopher Love,
Christina Alves, and Stephen Hadley
The biopharmaceutical industry’s preference for CHO cells reflects early collaborative efforts to develop the technologies and systems needed to use CHO cells on an industrial scale. Using a precompetitive, “open-access” model that harkens back to those collaborative roots, the AltHost Consortium seeks to build a library of customizable, nonmammalian eukaryotic cells for biopharmaceutical applications. Freelance contributor Gareth Macdonald and BPI’s Cheryl Scott spoke with leaders of the consortium this past spring to learn how yeast, fungi, and microalgae could provide for more agile production processes with greater volumetric productivity than that offered by CHO.

Cell-Free Expression: A Technology with Truly Disruptive Potential
by Cheryl Scott, with Beatrice Melinek
Following up on BPI’s first technical article on cell-free synthesis, published in September 2020, BPI’s senior technical editor herein speaks with Beatrice Melinek (postdoctoral research fellow at University College London’s Future Targeted Healthcare Manufacturing Hub). Scott and Melinek compare the capabilities of cell-free protein expression with those of CHO cells and other cell-based systems. Their discussion also calls attention to what researchers need to do to make cell-free synthesis an effective, cost-competitive alternative to CHO.

Technologies and Innovations: A Discussion with Selexis SA
by BPI Staff, with Pierre-Alain Girod
Cell-line engineering has advanced dramatically over the past decade, with new promoters and instrumentation transforming workflows. In this supplier-side article, the chief scientific officer of Selexis SA explains his company’s approaches to developing high-expression vectors, improving clone selection using novel single-cell–isolating instruments, and optimizing cell-line development workflows.