期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 42, 页码 E9944-E9952出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1811276115
关键词
nanoparticle; CRISPR; RNAi; barcoded nanoparticle; mRNA
资金
- Georgia Tech startup funds
- NIH/National Institute of General Medical Sciences (NIGMS) [T32EB021962]
- Georgia Research Assistantship Grant [3201330]
- NIH/NIGMS [T32GM008433]
- National Institutes of Health GT BioMAT Training Grant [5T32EB006343]
- Cystic Fibrosis Research Foundation [DAHLMA15XX0]
- Parkinson's Disease Foundation [PDF-JFA-1860]
- Bayer Hemophilia Awards Program AGE DTD
Dysfunctional endothelium causes more disease than any other cell type. Systemically administered RNA delivery to nonliver tissues remains challenging, in large part because there is no high-throughput method to identify nanoparticles that deliver functional mRNA to cells in vivo. Here we report a system capable of simultaneously quantifying how >100 lipid nanoparticles (LNPs) deliver mRNA that is translated into functional protein. Using this system (named FIND), we measured how > 250 LNPs delivered mRNA to multiple cell types in vivo and identified 7C2 and 7C3, two LNPs that efficiently deliver siRNA, single-guide RNA (sgRNA), and mRNA to endothelial cells. The 7C3 delivered Cas9 mRNA and sgRNA to splenic endothelial cells as efficiently as hepatocytes, distinguishing it from LNPs that deliver Cas9 mRNA and sgRNA to hepatocytes more than other cell types. These data demonstrate that FIND can identify nanoparticles with novel tropisms in vivo.
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