Efficient Intracellular Delivery of CRISPR-Cas Ribonucleoproteins through Receptor Mediated Endocytosis.
ACS Chem Biol
; 14(3): 554-561, 2019 03 15.
Article
em En
| MEDLINE
| ID: mdl-30779874
ABSTRACT
We recently reported a new delivery system harnessing surface receptors for targeted uptake of CRISPR-Cas9 ribonucleoprotein into mammalian cells (Rouet et al., JACS 2018). For this purpose, Cas9 protein was labeled with the small molecule ligand ASGRL, specific for the asialoglycoprotein receptor, enabling endosomal uptake of the ribonucleoprotein into human cells expressing the receptor. However, detailed mechanistic insights had remained unknown and editing efficiency low. Here we investigate the mechanism of endosomal escape as mediated by the ppTG21 endosomolytic peptide and outline the development of novel Cas9 or Cas12a ribonucleoprotein complexes with increased editing efficiency.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Ribonucleoproteínas
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Endocitose
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Proteínas Associadas a CRISPR
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Sistemas CRISPR-Cas
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article