期刊
ACS NANO
卷 14, 期 4, 页码 4727-4740出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c00602
关键词
RNA origami; RNA nanostructures; TLR3 agonists; peritoneal metastatic colon cancer; cancer immunotherapy
类别
资金
- Office of Naval Research [N000141512689]
- National Science Foundation [1360635, 1563799, 1334109]
- ASU Women & Philanthropy grant ASU SOLS/OKED Research Investment Fund
- ASU Catalyst Fund
- U.S. Department of Defense (DOD) [N000141512689] Funding Source: U.S. Department of Defense (DOD)
- Direct For Computer & Info Scie & Enginr
- Division of Computing and Communication Foundations [1563799] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1360635] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1334109] Funding Source: National Science Foundation
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.
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