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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
PubMed

Insights

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 therapy

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