High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing.
Proc Natl Acad Sci U S A
; 115(42): E9944-E9952, 2018 10 16.
Article
en En
| MEDLINE
| ID: mdl-30275336
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ARN Mensajero
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ARN Guía de Kinetoplastida
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Técnicas de Transferencia de Gen
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Células Endoteliales
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Nanopartículas
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Sistemas CRISPR-Cas
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Edición Génica
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Lípidos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article