Open AccessEndosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework
Author(s) -
Shahad K. Alsaiari,
Sachin Patil,
Mram Alyami,
Kholod Alamoudi,
Fajr A. Aleisa,
Jasmeen S. Merzaban,
Mo Li,
Niveen M. Khashab
Publication year - 2017
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.7b11754
Subject(s) - crispr , cas9 , genome editing , chemistry , subgenomic mrna , imidazolate , nanotechnology , nanoscopic scale , zeolitic imidazolate framework , gene , biochemistry , materials science , inorganic chemistry , organic chemistry , adsorption , metal organic framework
CRISPR/Cas9 is a combined protein (Cas9) and an engineered single guide RNA (sgRNA) genome editing platform that offers revolutionary solutions to genetic diseases. It has, however, a double delivery problem owning to the large protein size and the highly charged RNA component. In this work, we report the first example of CRISPR/Cas9 encapsulated by nanoscale zeolitic imidazole frameworks (ZIFs) with a loading efficiency of 17% and enhanced endosomal escape promoted by the protonated imidazole moieties. The gene editing potential of CRISPR/Cas9 encapsulated by ZIF-8 (CC-ZIFs) is further verified by knocking down the gene expression of green fluorescent protein by 37% over 4 days. The nanoscale CC-ZIFs are biocompatible and easily scaled-up offering excellent loading capacity and controlled codelivery of intact Cas9 protein and sgRNA.
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