Stabilized Interleukin-6 receptor binding RNA aptamers.

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine that is involved in the progression of various inflammatory diseases, such as rheumatoid arthritis and certain cancers; for example, multiple myeloma or hepatocellular carcinoma. To interfere with IL-6-dependent diseases, targeting IL-6 receptor (IL-6R)-presenting tumor cells using aptamers might be a valuable strategy to broaden established IL-6- or IL-6R-directed treatment regimens. Recently, we reported on the in vitro selection of RNA aptamers binding to the human IL-6 receptor (IL-6R) with nanomolar affinity. One aptamer, namely AIR-3A, was 19 nt in size and able to deliver bulky cargos into IL-6R-presenting cells. As AIR-3A is a natural RNA molecule, its use for in vivo applications might be limited due to its susceptibility to ubiquitous ribonucleases. Aiming at more robust RNA aptamers targeting IL-6R, we now report on the generation of stabilized RNA aptamers for potential in vivo applications. The new 2'-F-modified RNA aptamers bind to IL-6R via its extracellular portion with low nanomolar affinity comparable to the previously identified unmodified counterpart. Aptamers do not interfere with the IL-6 receptor complex formation. The work described here represents one further step to potentially apply stabilized IL-6R-binding RNA aptamers in IL-6R-connected diseases, like multiple myeloma and hepatocellular carcinoma.

• Authors: Cindy Meyer, Katharina Berg, Katja Eydeler-Haeder, Inken Lorenzen, Joachim Grötzinger, Stefan Rose-John, Ulrich Hahn
• Journal: RNA biology (RNA Biol) Vol. 11 Issue 1 Pg. 57-65 ( 2014) ISSN: 1555-8584 [Electronic] United States
• PMID: 24440854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aptamers, Nucleotide
• Fluoresceins
• Receptors, Interleukin-6
• RNA

Topics

• Aptamers, Nucleotide (chemistry, metabolism)
• Fluoresceins
• Humans
• Neoplasms (genetics, metabolism)
• Protein Binding
• RNA (chemistry, genetics)
• RNA Stability
• Receptors, Interleukin-6 (metabolism)