Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor

International Journal of Molecular Sciences
David S LeeDaniel E Johnson

Abstract

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.

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Citations

Sep 19, 2019·Cancers·Yoojung KwonDooil Jeoung
Nov 2, 2019·Cancers·Yue-Ting K LauJennifer R Grandis
Nov 19, 2020·Molecular Cancer Therapeutics·Jamie V ShiahDaniel E Johnson
Apr 10, 2021·Cell Chemical Biology·Kusal T G SamarasingheCraig M Crews
Sep 11, 2021·Journal of Translational Medicine·Jianyuan PanYongqin Tang

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Methods Mentioned

BETA
antisense oligodeoxynucleotide
pull-down
electrophoresis
pull down
enzymatic ligation

Clinical Trials Mentioned

NCT03421353

Software Mentioned

GraphPad Prism
Image Studio Lite
CS3D

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