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Open AccessArticle

Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor

1
School of Medicine, University of California at San Francisco, San Francisco, CA 94115, USA
2
Department of Otolaryngology—Head and Neck Surgery, University of California at San Francisco, San Francisco, CA 94115, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(6), 1608; https://doi.org/10.3390/ijms19061608
Received: 27 April 2018 / Accepted: 29 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Advances in Biological Functions of STAT3)
Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials. View Full-Text
Keywords: STAT3 as a drug target; cyclic STAT3 decoy; oligodeoxynucleotide inhibitor; head and neck cancer STAT3 as a drug target; cyclic STAT3 decoy; oligodeoxynucleotide inhibitor; head and neck cancer
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MDPI and ACS Style

Lee, D.S.; O’Keefe, R.A.; Ha, P.K.; Grandis, J.R.; Johnson, D.E. Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor. Int. J. Mol. Sci. 2018, 19, 1608.

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