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RNA Origami Nanostructures for Potent and Safe Anticancer Immunotherapy.

Xiaodong QiXiaowei LiuLawrence MatiskiRyan Rodriguez Del VillarTheresa YipFei ZhangSriram SokalingamShuoxing JiangLi LiuHao YanYung Chang
Published in: ACS nano (2020)
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.
Keyphrases
  • nucleic acid
  • toll like receptor
  • immune response
  • inflammatory response
  • small cell lung cancer
  • signaling pathway
  • risk assessment
  • human health