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

Shahad K. Alsaiari, Sachin Patil, Mram Z. Alyami, Kholod Alamoudi, Fajr A Aleisa, Jasmeen Merzaban, Mo Li, Niveen M. Khashab

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216 Scopus citations


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 employing CRISPR/Cas9 machinery. The nanoscale CC-ZIFs are biocompatible and easily scaled-up offering excellent loading capacity and controlled co-delivery of intact Cas9 protein and sgRNA.
Original languageEnglish (US)
Pages (from-to)143-146
Number of pages4
JournalJournal of the American Chemical Society
Issue number1
StatePublished - Dec 27 2017

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