Sabrina Wildner

Abstract

Biopharmaceuticals (biologics) are protein molecules produced in living cells and used in therapy for a wide range of disorders like cancer, autoimmune or autoinflammatory diseases. In contrast to small molecule drugs, biologics are highly sensitive to their manufacturing and handling conditions. The production of biopharmaceutical drugs in living cells can thus result in minor conformational differences due to posttranslational modifications, different codon usage, etc. These subtle conformational changes can however impact the safety, efficacy and stability of the product and can remain undetected by analytical methods. A new tool termed aptamers can help to detect changes in three-dimensional structures of biopharmaceutical products. Aptamers are short, single-stranded oligonucleotides which can adopt specific three dimensional shapes. SELEX (systematic evolution of ligands by exponential enrichment) is a technique for screening large oligonucleotide libraries and is used for in vitro selection and amplification. My aim is to select a panel of aptamers reactive against an antibody-based biopharmaceutical. Aptamers can be used as surrogate antibodies in ELISA assays to characterize potential conformational differences between originator and biosimilar, monitor a production process or determine structural changes during shelf life of a product.