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RNA Biol. 2014;11(1):57-65. doi: 10.4161/rna.27447. Epub 2013 Dec 20.

Stabilized Interleukin-6 receptor binding RNA aptamers.

Author information

1
Laboratory of RNA Molecular Biology; Howard Hughes Medical Institute; The Rockefeller University; New York, NY USA.
2
Institute of Biochemistry and Molecular Biology; Chemistry Department; MIN-Faculty; Hamburg University; Hamburg, Germany.
3
Institute of Biochemistry; Medical Faculty; Christian-Albrechts-University; Kiel, Germany.

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.

KEYWORDS:

Aptamers; Hyper-IL-6; Interleukin-6 receptor; RNA; RNA-protein interaction; SELEX; post-selective modification

PMID:
24440854
PMCID:
PMC3929425
DOI:
10.4161/rna.27447
[Indexed for MEDLINE]
Free PMC Article
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