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. 2018 Jan 10;140(1):143-146.
doi: 10.1021/jacs.7b11754. Epub 2017 Dec 27.

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework

Shahad K Alsaiari  1 , Sachin Patil  1 , Mram Alyami  1 , Kholod O Alamoudi  1 , Fajr A Aleisa  2 , Jasmeen S Merzaban  2 , Mo Li  3 , Niveen M Khashab  1
Affiliations

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework

Shahad K Alsaiari et al. J Am Chem Soc. .

Abstract

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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