Production of NIIMBL’s Antibodies in the Thermothelomyces Heterothallica Cl Expression System

This project will execute a demonstration of the use of the C1 Protein Production Platform for the rapid engineering of production strains to produce a COVID-19 targeted antibody as well as a monoclonal antibody used as a standard for comparability.

Industry Need

Chinese Hamster Ovary (CHO) cells are the most common host platform for producing antibodies. While there is widespread adoption of this platform, there remain limitations to the use of CHO cells in certain applications, in particular to produce antibodies at large scale to combat infectious diseases:

The doubling-time of CHO cells leads to protracted scale-up stages using multiple fermenter scales as seed trains
The cell density and overall specific productivity of CHO cells remain low
The growth and production media used in production is expensive

Solution

Using a C1 Protein Production Platform (a Thermophilici Filamentous Fungus Thermothelomyces heterothallica based platform), Dyadic International, Inc. demonstrated the use of a new platform for rapid engineering of product strains to produce a COVID-19 targeted antibody and a monoclonal antibody used as a standard for comparability. Dyadic benchmarked the C1 Protein Production Platform performance in comparison to CHO and other fungal expression systems in terms of speed of development and certain product quality attributes.

As part of the solution, once antibody gene sequences are received, the team:

Constructed them into expression vectors to be transformed into multiple C1-based strains
Grew a select set of transformants
Analyzed the products of the target protein
Selected the best performing clones for lab-scale fermentation to isolate and purify the target protein for antibody analysis

Outcomes and Impacts

By benchmarking the innovative, state of the art C1 Protein Production Platform versus legacy protein production methods, Dyadic discovered that the production system could potentially lead to the development of C1 based production strains for the rapid production of large quantities of lower-cost vaccine antigens and antibodies in response to pandemics and other environmental and man-made health threats.

The Thermothelomyces heterthalica C1 production system has great potential for use in responding to future pandemics because the production cell lines can be constructed quickly, and the antibodies have good productivity.

Updates, Related Publications, and Deliverables

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Project Lead

Dyadic International Inc