Chinese hamster ovary (CHO) and other mammalian cells are fragile, finicky, and “high maintenance.” Anyone who has worked with them knows well their many culture requirements. Such cells are also vulnerable to environmental stresses and to attack by adventitious agents. CHO’s capability for assembling complex proteins in increasingly large amounts would seem to make up for the platform’s many needs and susceptibilities. But drug developers are turning increasingly to alternative hosts for therapeutic-protein expression, hoping to leverage the easier and less resource-intensive culture requirements of plants and microbes for scalable, cost-effective biologics production. Such platforms also are beginning to produce complex proteins with human-like glycosylation patterns. The articles in this month’s featured report highlight recent efforts to bring plant, microbial, and other alternative protein-expression systems to the fore of the biopharmaceutical industry.      

Introduction: The Next Big Thing Could Be Disruptive
Cheryl Scott
BPI’s senior technical editor sets the stage for the other articles in the report by overviewing the advantages and limitations of CHO cells for expression of therapeutic proteins. She points out that although biopharmaceutical companies often tout their technologies as paradigm disrupting, recent advances in plant- and microbe-based expression could very well change how the industry approaches biologics production.

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Reinventing How Drugs Are Invented: Making a Case for Simplicity in Drug Development and Production
Brian Finrow (cofounder and CEO of Lumen Biosciences)
The biopharmaceutical industry finds itself in the throes of a “creativity crisis,” with research and development (R&D) productivity continuing along a downward trend that began in the late 1990s. Finrow suggests that, to climb out of the R&D rut, drug companies must learn from healthier industries that excel in product development. A particularly important lesson is to simply production platforms. In this article, Finrow explains how his company uses spirulina, an edible cyanobacteria biomass, to express therapeutic proteins for oral administration. The process, he shows, reduces biomanufacturing complexity significantly compared with that involved with mammalian-cell protein expression. In turn, spirulina-based production drives down costs and makes therapies more accessible to patients.

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Leveraging Plant-Based Protein Expression: Implications for Biologics Manufacturing and Biodefense
Brian Gazaille, with Don Stewart (cofounder and CEO of PlantForm Corporation and AntoXa)
AntoXa Corporation is a Canadian biopharmaceutical company that specializes in developing medical countermeasures to bioterrorist attacks and pandemics. Among several active programs, the company is producing a monoclonal antibody (MAb) for therapy for exposure to ricin, a potentially lethal molecule that has been used a bioterrorist agent. Of particular note is that the organization leverages technologies for plant-based expression of therapeutic proteins. Herein, BPI’s managing editor speaks with the cofounder and chief executive of both AntoXa and its parent company, PlantForm, to learn about advances in plant-based production platforms and Agrobacteria expression vectors. Such production strategies hold significant promise for manufacturing proteins quickly, safely, and at low costs, all of which are essential when responding to biosecurity threats

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Designer Cells for In Vivo Expression of Therapeutic Proteins: Emerging Applications Based on Gene Circuits
Brian Gazaille, with Martin Fussenegger (professor of biotechnology and bioengineering, Department of Biosystems Science and Engineering (D-​BSSE), ETH Zurich)
Scientists have a wealth of options for enhancing cell-line engineering activities, including techniques for knocking target genes in, out, down, or up. But as BPI’s managing editor learns in this interview with an ETH Zurich professor of bioengineering, such methods do not empower cells to respond dynamically to multifarious conditions during cell culture or in vivo application. Here, synthetic biology could prove especially useful. Insertion of gene circuits (complex genetic networks) into human cells could improve drug developers’ control over cell metabolism, gene expression, and related activities. Using such networks, cells can be programmed to sense disease-related biomarkers and generate tunable therapeutic responses. The approach holds much promise for development of cell-based therapies, including treatments that express therapeutic biomolecules in vivo.

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