Home
Resources
Publications
In Situ Repurposing of Dendritic Cells With CRISPR/Cas9-based Nanomedicine to Induce Transplant Tolerance

In Situ Repurposing of Dendritic Cells With CRISPR/Cas9-based Nanomedicine to Induce Transplant Tolerance

Yue Zhang, Song Shen, Gui Zhao, Cong-Fei Xu, Hou-Bing Zhang, Ying-Li Luo, Zhi-Ting Cao, Jia Shi, Zhi-Bin Zhao, Zhe-Xiong Lian, Jun Wang

Biomaterials. 2019 Oct;217:119302.

PMID: 31271858

Abstract:

Organ transplantation is the only effective method to treat end-stage organ failure. However, it is continuously plagued by immune rejection, which is mostly caused by T cell-mediated reactions. Dendritic cells (DCs) are professional antigen-presenting cells, and blocking the costimulatory signaling molecule CD40 in DCs inhibits T cell activation and induces transplant tolerance. In this study, to relieve graft rejection, Cas9 mRNA (mCas9) and a guide RNA targeting the costimulatory molecule CD40 (gCD40) were prepared and encapsulated into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-b-PLGA)-based cationic lipid-assisted nanoparticles (CLAN), denoted CLANmCas9/gCD40. CLAN effectively delivered mCas9/gCD40 into DCs and disrupted CD40 in DCs at the genomic level both in vitro and in vivo. After intravenous injection into an acute mouse skin transplant model, CLANmCas9/gCD40-mediated CD40 disruption significantly inhibited T cell activation, which reduced graft damage and prolonged graft survival. This work provides a promising strategy for reprogramming DCs with nanoparticles carrying the CRISPR/Cas9 system to abate transplant rejection.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS74336	Poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide)			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: