Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework
AuthorsAlsaiari, Shahad K.
Alyami, Mram Z.
Aleisa, Fajr A
Khashab, Niveen M.
KAUST DepartmentAdvanced Membranes and Porous Materials Research Center
Smart Hybrid Materials (SHMs) lab
Biological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/626437
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AbstractCRISPR/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.
CitationAlsaiari SK, Patil S, Alyami M, Alamoudi K, Aleisa fajr, et al. (2017) Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework. Journal of the American Chemical Society. Available: http://dx.doi.org/10.1021/jacs.7b11754.
PublisherAmerican Chemical Society (ACS)
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