Engineered Extracellular Vesicle-Delivered CRISPR/CasRx as a Novel RNA Editing Tool

Tianwen Li, Liansheng Zhang, Tao Lu, Tongming Zhu, Canbin Feng, Ni Gao, Fei Liu, Jingyu Yu, Kezhu Chen, Junjie Zhong, Qisheng Tang, Quan Zhang, Xiangyang Deng, Junwei Ren, Jun Zeng, Haibo Zhou*, Jianhong Zhu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide-optimized and EVs-delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)-triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short-acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

Original languageEnglish
Article number2206517
JournalAdvanced Science
Volume10
Issue number10
DOIs
Publication statusPublished - 5 Apr 2023
Externally publishedYes

Keywords

  • CRISPR/CasRx
  • RNA editing
  • extracellular vesicles
  • inflammatory disease

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