BIOTECHNOLOGY
FROMLLAMAS TOYEAST
Producing functional therapeutic antibody fragments in Saccharomyces cerevisiae
S
ince 2021, Phenotypeca has been collaborating with Isogenica in an IUK-funded project worth up to £400,000 to design, produce and test therapeutic antibody fragments. Isogenica is an expert in developing small antibody fragments (VHHs). During its 20-year history, Isogenica has established successful discovery partnerships with biopharma companies across the globe, as well as research collaborations with other SMEs and academic groups.
VHHs have been on the radar of life scientists and medical practitioners for their use in clinical therapeutics and immunodiagnostics since their discovery in llamas and other camelids in the early 1990s, with the first VHH-based therapeutic – caplacizumab – approved in 2019. Biotherapeutics are most commonly manufactured in mammalian systems due to their complexity. Tese molecules, such as conventional antibodies or cytokines,
contain multiple domains and often require distinct glycosylation patterns. VHHs are approximately 1/10th the size of conventional antibodies and generally do not require glycosylation, making them more straightforward to manufacture in microbial systems.
Although these molecules can be
produced in E. coli for early-stage research, the presence of endotoxins makes this material unsuitable for later stage assays, while mammalian cell production systems are often prohibitively expensive, and it is challenging to increase throughput. Caplacizumab is manufactured in the yeast Pichia pastoris. However, this yeast strain is fed by methanol, which has both toxicity risks and poses fire hazards during large- scale manufacture. Tis presents a market opportunity for alternative bioproduction hosts with low cost of goods. Phenotypeca has the world’s largest unique collection of Saccharomyces cerevisiae strains bred and engineered for stable recombinant protein production. By transitioning early R&D to a final manufacturing host, drug discovery
Phenotypeca’s platform is helping to develop a bright future for VHHs
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