Aptamers for the detection of glycosylation changes – AptaGlyc

Diagnostics of immune diseases based on altered sugar structures

Sugar structures are ubiquitous in the human body. They surround the cells like a scaffold to protect them on the one hand and to enable interactions with other compartments on the other hand. The so-called glycans occur as glycolipids, proteoglycans or glycoproteins. Glycosylation is a complex posttranslational modification involving many different enzymes. The structural complexity of oligosaccharides allows them to function as information carriers. Many proteins have specific sugar structures that contribute decisively to the function of the protein.

Disease status influences protein glycosylation

© Fraunhofer IAP

Structurally altered protein glycosylation can be an important indicator for the diagnosis of autoimmune diseases. It is known that the glycosylation of immunoglobulins (Ig) is age- and gender-dependent, but also changes with the disease status. In the case of autoimmune disease, the ratio shifts towards shorter glycan chains. Important examples are rheumatoid arthritis and IgA nephropathy. It is still unclear to what extent the glycosylation changes during the development of the disease until its onset. With this knowledge, it would be possible to detect autoimmune diseases at an early stage in order to be able to treat affected patients as quickly and efficiently as possible. The detection of altered glycosylation patterns, which would allow diagnosis or even early detection, is currently underused due to the extremely complex analysis.

Identification of protein glycosylation by recognition molecules and a fluorescence-based detection system

© Fraunhofer IZI-BB

The aim of the project is to identify relevant sugar structures by nucleic acid-based recognition molecules (aptamers) and to convert them into an easily measurable signal. Aptamers are short-chain single-stranded DNA or RNA nucleic acids that can bind highly specific target structures due to their sequence-dependent 3D structure. Sugar-binding aptamers are identified in an automated selection procedure based on magnetic particles. A structural change of the aptamers associated with the binding of the aptamer to the target molecule will be used for a simple fluorescence-based detection system.

Development of a novel technology for the diagnosis of immune diseases

This project lays the groundwork for a technology to diagnose immune disorders associated with changes in the glycosylation patterns of antibodies or other proteins. Since glycosylation can be altered well before the onset of the disease, early detection of these diseases is also possible. At the beginning, rheumatoid arthritis is the main focus. If successful, it may even be possible to monitor the progress of treatment using this glycan analysis. Beyond the diagnosis of glycan-associated diseases, applications are possible in the quality control of antibodies as well as active substances whose glycosylation is indispensable for their efficacy. This can replace the use of complex analytics.

Interdisciplinary collaboration

The project will make a contribution in the field of biomarker and drug analysis. The competencies of the Fraunhofer IAP (glycobiotechnology) and the Fraunhofer IZI-BB (aptamers) will be combined.

Fraunhofer IAP: Provision and modification of relevant sugar structures, glycan analytics

Fraunhofer IZI-BB: Development, characterization and optimization of aptamers



The development of aptamers that are able to bind sugar structures in a targeted and highly affinitive way would be a major step forward in aptamer research. In order to significantly simplify the diagnosis of immune diseases, the applicability of the system to clinical samples must be demonstrated. In addition, the technology has great application potential for the analysis and quality assurance of glycosylated active substances. To this end, the system will be extended by other target sugar structures in order to create a portfolio with which individual glycan structures can be detected.