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

Abstract

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.

• Authors: Nianan Luo, Jiangbin Li, Yafeng Chen, Yan Xu, Yu Wei, Jianguo Lu, Rui Dong
• Journal: Drug delivery (Drug Deliv) Vol. 28 Issue 1 Pg. 10-18 (Dec 2021) ISSN: 1521-0464 [Electronic] England
• PMID: 33336604 (Publication Type: Journal Article)

Chemical References

• Drug Carriers

Topics

• Animals
• CRISPR-Cas Systems (genetics)
• Cell Line
• Drug Carriers
• Exosomes (physiology)
• Gene Editing (methods)
• Hepatic Stellate Cells (physiology)
• Humans
• Mice
• Mice, Inbred C57BL