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Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of CRISPR/dCas9-SAM system - supplementary files

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posted on 2022-11-03, 14:18 authored by Nianan Luo, Wenjun Zhong, Jiangbin Li, Zhongjie Zhai, Jianguo Lu, Rui Dong

Aim: Hepatic fibrosis is one of the most common conditions worldwide, and yet no effective antifibrotic

therapy is available. This study aimed to reverse hepatic fibrosis via exosome-mediated delivery of the

CRISPR/dCas9-SAM system. Materials & methods: The authors constructed a modified-exosome delivery

system targeting hepatic stellate cells (HSCs), and constructed the CRISPR/dCas9-SAM system inducing

HSCs convert into hepatocyte-like cells in vitro and in vivo. Results: RBP4-modified exosomes could

efficiently load and deliver the CRISPR/dCas9 system to HSCs. The in vitro CRISPR/dCas9 system induced

the conversion from HSCs to hepatocyte-like cells via targeted activation of HNF4α/HGF1/FOXA2 genes.

Importantly, in vivo targeted delivery of this system significantly attenuated CCl4-induced hepatic fibrosis.

Conclusion: Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated

delivery of the CRISPR/dCas9-SAM system, which provides a feasible antifibrotic strategy.

Funding

Shaanxi Social Development Fund, (Grant / Award Number: '2020SF-067'

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