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Programmable Circular Single-Stranded DNA Acts as Recyclable Anti-miRNA Nucleotides to Inhibit Colorectal Cancer
Jinghao Wang1,2, Pengfei Zhang2,3,4, Guang Hu2,5
1Department of Chemistry, University of Science & Technology of China, Hefei, Anhui, China.
Small Methods
|May 13, 2026
Summary
This study introduces circular single-stranded DNA (CssDNA) as a novel platform for colorectal cancer (CRC) therapy. CssDNA effectively targets multiple oncomiRs, restoring tumor suppressor gene expression and offering a stable, recyclable treatment option.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- MicroRNA (miRNA) therapy shows promise for colorectal cancer (CRC) treatment.
- Targeting single oncomiRs has limited efficacy due to simultaneous action of multiple oncomiRs in CRC.
- Current anti-miRNA nucleotide (AMiN) designs face challenges like high synthetic error rates and difficulty in synthesizing long oligonucleotides.
Purpose of the Study:
- To develop a novel, stable, and recyclable multi-oncomiR targeting platform for colorectal cancer (CRC) therapy.
- To utilize circular single-stranded DNA (CssDNA) as a superior alternative to conventional AMiNs.
- To demonstrate the efficacy of CssDNA in degrading multiple oncomiRs and restoring tumor suppressor gene (TSG) expression.
Main Methods:
- Development of a multi-oncomiR targeting platform using in vivo M13 phage-generated circular single-stranded DNA (CssDNA).
- CssDNA designed to act as a sponge, attracting and degrading multiple overexpressed oncomiRs in CRC.
- Assessment of CssDNA's stability, low immunogenicity, recyclability, and efficacy in promoting TSG expression.
Main Results:
- Engineered CssDNA demonstrated high stability, low immunogenicity, and potential for long oligonucleotide synthesis.
- CssDNA effectively sponged and degraded multiple oncogenic miRNAs (oncomiRs) in colorectal cancer models.
- Degradation of oncomiRs led to the restoration of tumor suppressor gene (TSG) expression, inhibiting CRC progression.
- Released CssDNA exhibited recyclability, enabling a second round of therapeutic action.
Conclusions:
- Circular single-stranded DNA (CssDNA) presents a promising, stable, and recyclable platform for multi-oncomiR targeting in colorectal cancer (CRC) therapy.
- This novel CssDNA-based approach offers advantages over traditional anti-miRNA nucleotide (AMiN) designs.
- The sequence-customizable CssDNA platform holds potential for antagonizing miRNA-mediated repression of tumor suppressor genes in various cancer treatments.
Keywords:
DNA‐based nanomedicinesanti‐miRNA nucleotidecircular single‐stranded DNAmicroRNAmulti‐targeted therapyMore Related Videos
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