RNA Origami Nanostructures for Potent and Safe Anticancer Immunotherapy

Xiaodong Qi, Xiaowei Liu, Lawrence Matiski, Ryan Rodriguez Del Villar, Theresa Yip, Fei Zhang, Sriram Sokalingam, Shuoxing Jiang, Li Liu, Hao Yan, Yung Chang

Research output: Contribution to journalArticle

Abstract

Rapid developments in nucleic acid nanotechnology have enabled the rational design and construction of self-assembling DNA and RNA nanostructures that are highly programmable. We recently developed a replicable single-stranded RNA origami (RNA-OG) technology that allows a long RNA molecule to be programmed to self-assemble into nanostructures of various shapes. Here, we show that such RNA-OG is highly stable in serum/plasma, and we thus exploited its immunostimulatory potential. We demonstrated that the RNA-OG stimulates a potent innate response primarily through a Toll-like receptor 3 (TLR3) pathway. In a murine peritoneal metastatic colon cancer model, intraperitoneally injected RNA-OG induced significant tumor retardation or regression by activating NK- and CD8-dependent antitumor immunity and antagonizing the peritoneal immunosuppressive environment. Unlike polyinosinic/polycytidylic acid (PolyIC), a well-known double-stranded RNA analogue, the RNA-OG treatment did not cause a high level of type-I interferons in the blood nor apparent toxicity upon its systemic administration in the animals. This work establishes the function of RNA-OG as a potent line of TLR3 agonists that are safe and effective for cancer immunotherapy.

Original languageEnglish
Pages (from-to)4727-4740
Number of pages14
JournalACS nano
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 28 2020

Keywords

  • cancer immunotherapy
  • peritoneal metastatic colon cancer
  • RNA nanostructures
  • RNA origami
  • TLR3 agonists

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Qi, X., Liu, X., Matiski, L., Rodriguez Del Villar, R., Yip, T., Zhang, F., Sokalingam, S., Jiang, S., Liu, L., Yan, H., & Chang, Y. (2020). RNA Origami Nanostructures for Potent and Safe Anticancer Immunotherapy. ACS nano, 14(4), 4727-4740. https://doi.org/10.1021/acsnano.0c00602