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

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    Name:
    jacs.7b11754.pdf
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    625.7Kb
    Format:
    PDF
    Description:
    Accepted Manuscript
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    Type
    Article
    Authors
    Alsaiari, Shahad K. cc
    Patil, Sachin cc
    Alyami, Mram Z. cc
    Alamoudi, Kholod cc
    Aleisa, Fajr A cc
    Merzaban, Jasmeen cc
    Li, Mo cc
    Khashab, Niveen M. cc
    KAUST Department
    Advanced Membranes and Porous Materials Research Center
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Chemical Science Program
    Physical Science and Engineering (PSE) Division
    Smart Hybrid Materials (SHMs) lab
    Date
    2017-12-27
    Online Publication Date
    2017-12-27
    Print Publication Date
    2018-01-10
    Permanent link to this record
    http://hdl.handle.net/10754/626437
    
    Metadata
    Show full item record
    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 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.
    Citation
    Alsaiari 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.
    Publisher
    American Chemical Society (ACS)
    Journal
    Journal of the American Chemical Society
    DOI
    10.1021/jacs.7b11754
    PubMed ID
    29272114
    Additional Links
    http://pubs.acs.org/doi/10.1021/jacs.7b11754
    ae974a485f413a2113503eed53cd6c53
    10.1021/jacs.7b11754
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Advanced Membranes and Porous Materials Research Center; Physical Science and Engineering (PSE) Division; Controlled Release and Delivery Laboratory; Chemical Science Program

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