期刊
ACS CHEMICAL BIOLOGY
卷 14, 期 3, 页码 554-561出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.9b00116
关键词
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资金
- Australian National Health and Medical Research Council
- NHMRC [APP1090875]
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.
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