SomaLogic scientists and colleagues publish two papers describing IL-6 SOMAmers

SomaLogic scientists and colleagues publish two papers describing IL-6 SOMAmers


In a pair of papers published in the Journal of Biological Chemistry on January 12, 2014, a group of SomaLogic researchers and their colleagues at Otsuka Pharmaceuticals and Emerald Bio describe the development of new SOMAmer reagents that can block signaling by interleukin-6 (IL-6, a critical protein involved in inflammation and cancer), as well as the structural interaction of the two molecules. This work both confirms the unique protein-binding properties of SOMAmers and underlines their potential as a new class of therapeutic reagents.

Signaling by IL-6 through its cellular receptors is known to play a major role in a wide range of biological activities, including immune responses, blood cell development, and even the proliferation of different types of cancer. Because of its multiple effects in a range of diseases, the IL-6 signaling pathway has been the target of many pharmaceutical intervention strategies. However, there is a wide variation in patient responses to these different approaches, suggesting that targeting the actual signaling molecule itself could be an effective approach for patients who do not respond to these other therapies.

The SomaLogic team and their colleagues used the SELEX process to identify SOMAmers that could bind IL-6 with high affinity and block its ability to interact with its cellular receptors. These SOMAmers were then further optimized, and then shown to be effective inhibitors of IL-6 in a variety of settings. Furthermore, the optimized SOMAmers demonstrated significantly improved stability in human serum, underlining their potential as possible therapeutic reagents. Further research is underway.

In addition to the functional studies, the research team analyzed the crystal structure of the new SOMAmers bound to their IL-6 target protein. This analysis confirmed the unique binding properties of SOMAmers compared to traditional aptamers and other protein-binding molecules, a result of the incorporation of modified nucleic acids into the DNA backbone.

Manuscript links:

AD Gelinas et al. (2014) Crystal Structure of Interleukin-6 in Complex with a Modified Nucleic Acid Ligand. J. Biol. Chem. Jan 12, 2014 (epub ahead of print). MEDLINE link.

S Gupta et al. (2014) Chemically-Modified DNA Aptamers Bind Interleukin-6 with High Affinity and Inhibit Signaling by Blocking its Interaction with Interleukin-6 Receptor. J. Biol. Chem. Jan 12, 2014 (epub ahead of print). MEDLINE link.