Drug Delivery (Jan 2021)

Hepatic stellate cell reprogramming via exosome-mediated CRISPR/dCas9-VP64 delivery

  • Nianan Luo,
  • Jiangbin Li,
  • Yafeng Chen,
  • Yan Xu,
  • Yu Wei,
  • Jianguo Lu,
  • Rui Dong

DOI
https://doi.org/10.1080/10717544.2020.1850917
Journal volume & issue
Vol. 28, no. 1
pp. 10 – 18

Abstract

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Hepatic stellate cells (HSCs) play a crucial role in the progression of liver fibrosis, which can be considered as the specific therapeutic target of anti-fibrotic treatment. Targeted induction of HSCs to hepatocytes via delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system holds promise for hepatic fibrosis treatment. Our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could efficiently and successfully be delivered into the HSCs. In turn, the CRISPR/dCas9-VP64 system loaded in the exosomes can be efficiently released into the HSCs. As a proof-of-concept study, gRNA against hepatocyte nuclear factor 4α (HNF4α) together with the delivery of CRISPR/dCas9-VP64 system induced the HSCs to hepatocyte-like phenotype. In conclusion, our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could be functional in HSCs, emerging as a gene therapy strategy for hepatic fibrosis.

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