RNA Origami Nanostructures for Potent and Safe Anticancer Immunotherapy
| Autor: | Lawrence Matiski, Xiaowei Liu, Shuoxing Jiang, Theresa Yip, Li Liu, Fei Zhang, Hao Yan, Ryan Rodriguez Del Villar, Xiaodong Qi, Sriram Sokalingam, Yung Chang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
General Physics and Astronomy 02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Mice Cancer immunotherapy medicine Animals Immunologic Factors Nanotechnology General Materials Science General Engineering Rational design RNA Immunotherapy 021001 nanoscience & nanotechnology 0104 chemical sciences Nanostructures Poly I-C chemistry TLR3 Nucleic acid Systemic administration Cancer research 0210 nano-technology DNA |
| Zdroj: | ACS nano. 14(4) |
| ISSN: | 1936-086X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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