A smart multiantenna gene theranostic system based on the programmed assembly of hypoxia-related siRNAs
Xue Gong,
Haizhou Wang,
Ruomeng Li,
Kaiyue Tan,
Jie Wei,
Jing Wang,
Chen Hong,
Jinhua Shang,
Xiaoqing Liu (),
Jing Liu and
Fuan Wang ()
Additional contact information
Xue Gong: Wuhan University
Haizhou Wang: Wuhan University
Ruomeng Li: Wuhan University
Kaiyue Tan: Wuhan University
Jie Wei: Wuhan University
Jing Wang: Wuhan University
Chen Hong: Wuhan University
Jinhua Shang: Wuhan University
Xiaoqing Liu: Wuhan University
Jing Liu: Wuhan University
Fuan Wang: Wuhan University
Nature Communications, 2021, vol. 12, issue 1, 1-13
Abstract:
Abstract The systemic therapeutic utilisation of RNA interference (RNAi) is limited by the non-specific off-target effects, which can have severe adverse impacts in clinical applications. The accurate use of RNAi requires tumour-specific on-demand conditional activation to eliminate the off-target effects of RNAi, for which conventional RNAi systems cannot be used. Herein, a tumourous biomarker-activated RNAi platform is achieved through the careful design of RNAi prodrugs in extracellular vesicles (EVs) with cancer-specific recognition/activation features. These RNAi prodrugs are assembled by splitting and reconstituting the principal siRNAs into a hybridisation chain reaction (HCR) amplification machine. EVs facilitate the specific and efficient internalisation of RNAi prodrugs into target tumour cells, where endogenous microRNAs (miRNAs) promote immediate and autonomous HCR-amplified RNAi activation to simultaneously silence multiantenna hypoxia-related genes. With multiple guaranteed cancer recognition and synergistic therapy features, the miRNA-initiated HCR-promoted RNAi cascade holds great promise for personalised theranostics that enable reliable diagnosis and programmable on-demand therapy.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24191-9
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DOI: 10.1038/s41467-021-24191-9
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