Hepatic stellate cell reprogramming via exosome-mediated CRISPR/dCas9-VP64 delivery
| Autor: | Nianan Luo, Jiangbin Li, Yafeng Chen, Yan Xu, Yu Wei, Jianguo Lu, Rui Dong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Drug Delivery, Vol 28, Iss 1, Pp 10-18 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1071-7544 1521-0464 10717544 |
| DOI: | 10.1080/10717544.2020.1850917 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|