气候变化领域集成服务门户(CCPortal): Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3

CCPortal

DOI	10.1073/pnas.2020401118
	Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3
	Qiu M.; Glass Z.; Chen J.; Haas M.; Jin X.; Zhao X.; Rui X.; Ye Z.; Li Y.; Zhang F.; Xu Q.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Loss-of-function mutations in Angiopoietin-like 3 (Angptl3) are associated with lowered blood lipid levels, making Angptl3 an attractive therapeutic target for the treatment of human lipoprotein metabolism disorders. In this study, we developed a lipid nanoparticle delivery platform carrying Cas9 messenger RNA (mRNA) and guide RNA for CRISPR-Cas9–based genome editing of Angptl3 in vivo. This system mediated specific and efficient Angptl3 gene knockdown in the liver of wild-type C57BL/6 mice, resulting in profound reductions in serum ANGPTL3 protein, low density lipoprotein cholesterol, and triglyceride levels. Our delivery platform is significantly more efficient than the FDA-approved MC-3 LNP, the current gold standard. No evidence of off-target mutagenesis was detected at any of the nine top-predicted sites, and no evidence of toxicity was detected in the liver. Importantly, the therapeutic effect of genome editing was stable for at least 100 d after a single dose administration. This study highlights the potential of LNP-mediated delivery as a specific, effective, and safe platform for Cas9-based therapeutics. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Angptl3; CRISPR-Cas9 mRNA delivery; Genome editing; Lipid nanoparticles
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180406
作者单位	Department of Biomedical Engineering, Tufts University, Medford, MA 02155, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States
推荐引用方式 GB/T 7714	Qiu M.,Glass Z.,Chen J.,et al. Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3[J],2021,118(10).
APA	Qiu M..,Glass Z..,Chen J..,Haas M..,Jin X..,...&Xu Q..(2021).Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Qiu M.,et al."Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).