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Protecting microRNAs from RNase degradation with steric DNA nanostructures

H Qian1,2, C Y Tay1,3,4, M I Setyawati1

  • 1Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585 , Singapore . Email: cheltwd@nus.edu.sg ; ; Tel: +65 6516 7262.

Chemical Science
|April 29, 2017
PubMed

Insights

Researchers developed a DNA nanostructure to protect tumor-suppressive microRNAs from degradation, enabling effective delivery for potential colorectal cancer therapy. This novel approach overcomes a key challenge in microRNA-based treatments.

Area of Science:

  • Biotechnology and Nanomedicine
  • Molecular Biology and Genetics
  • Oncology and Cancer Therapeutics

Background:

  • Tumor-suppressive microRNAs hold significant therapeutic potential for cancer treatment.
  • Current microRNA delivery strategies are limited by the vulnerability of microRNAs to degradation by RNases in physiological environments.
  • This degradation poses a major bottleneck for the clinical application of microRNA-based therapies.

Purpose of the Study:

  • To develop a novel DNA nanostructure for the protection and delivery of tumor-suppressive microRNAs.
  • To demonstrate the efficacy of this nanostructure in shielding microRNA-145 from RNase degradation.
  • To evaluate the therapeutic potential of protected microRNA-145 in human colorectal cancer cells.

Main Methods:

  • Design and synthesis of a programmable, self-assembled DNA nanostructure with a 'shuriken' shape.
  • Incorporation of complementary sequences within the nanostructure to hybridize with microRNA cargo.
  • In vitro assessment of microRNA protection and delivery in human colorectal cancer cells.

Main Results:

  • The DNA nanostructure successfully protected microRNA-145 from RNase degradation through steric shielding.
  • The nanostructure facilitated the delivery of microRNA-145, allowing it to exert its therapeutic effect.
  • This proof-of-concept study validates the DNA nanostructure as a protective delivery vehicle for microRNAs.

Conclusions:

  • A novel DNA nanostructure-based approach effectively protects microRNAs from degradation, addressing a critical challenge in nucleic acid delivery.
  • This 'protector' concept offers a new paradigm for exploiting tumor-suppressive microRNAs in anti-cancer therapy.
  • The developed system shows promise for advancing microRNA-based therapeutics for colorectal cancer and potentially other malignancies.

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