Triple-Targeting Delivery of CRISPR/Cas9 to Reduce the Risk of Cardiovascular Diseases

Zhang, Lingmin2,3; Wang, Le2; Xie, Yangzhouyun2; Wang, Peng2; Deng, Sai3; Qin, Aiping3; Zhang, Jiangjiang2; Yu, Xiyong3; Zheng, Wenfu2; Jiang, Xingyu1,2,3,4

2019-08

10.1002/anie.201903618

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   影响因子和分区

1433-7851

1521-3773

A high level of low-density lipoprotein cholesterol (LDL-C) in the blood is a major risk factor for coronary heart disease. Herein, we present a triple-targeting strategy to generate a loss-of-function mutation in Pcsk9, which regulates plasma cholesterol levels, using a nanocarrier-delivered CRISPR/Cas9 system. Nuclear localization signal (NLS)-tagged Cas9 and Pcsk9-targeted single guide RNA (sgPcsk9) were complexed with gold nanoclusters (GNCs) modified with cationic HIV-1-transactivating transcriptor (TAT) peptide and further encapsulated in a galactose-modified lipid layer to target the nanoclusters to the liver. The resulting nanoclusters had an in vitro Pcsk9-editing efficiency of about 60 % and resulting in a decrease in plasma LDL-C in mice of approximately 30%. No off-target mutagenesis was detected in 10 sites with high similarity. This approach may have therapeutic potential for the prevention and treatment of cardiovascular disease without side effects.

CRISPR Cas9 gene editing drug delivery low-density lipoprotein cholesterol nanoparticles

SCI ; EI

英语

NI论文

通讯

Chinese Academy of Sciences[121D11KYSB20170026]

Chemistry

Chemistry, Multidisciplinary

WOS:000479164200001

WILEY-V C H VERLAG GMBH

20193207276200

Cardiology ; Cholesterol ; Controlled drug delivery ; Diseases ; Drug delivery ; Lipoproteins ; Mammals ; Nanoclusters ; Nanoparticles

Medicine and Pharmacology:461.6 ; Nanotechnology:761 ; Organic Compounds:804.1 ; Solid State Physics:933

CHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, 1088 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China
2.Natl Ctr NanoSci & Technol, CAS Ctr Excellence Nanosci, Beijing Engn Res Ctr BioNanotechnol, CAS Key Lab Biol Effects Nanomat & Nanosafety, 11 BeiYiTiao, Beijing 100190, Peoples R China
3.Guangzhou Med Univ, Affiliated Hosp 3&5, Guangdong Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis,Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

Zhang, Lingmin,Wang, Le,Xie, Yangzhouyun,et al. Triple-Targeting Delivery of CRISPR/Cas9 to Reduce the Risk of Cardiovascular Diseases[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2019,58(36):12404-12408.

Zhang, Lingmin.,Wang, Le.,Xie, Yangzhouyun.,Wang, Peng.,Deng, Sai.,...&Jiang, Xingyu.(2019).Triple-Targeting Delivery of CRISPR/Cas9 to Reduce the Risk of Cardiovascular Diseases.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,58(36),12404-12408.

Zhang, Lingmin,et al."Triple-Targeting Delivery of CRISPR/Cas9 to Reduce the Risk of Cardiovascular Diseases".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 58.36(2019):12404-12408.