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Cell-Type-Specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks
Journal of the American Chemical Society ( IF 14.695 ) Pub Date : 2020-01-17 , DOI: 10.1021/jacs.9b11638
Mram Z. Alyami; Shahad K. Alsaiari; Yanyan Li; Somayah S. Qutub; Fajr A. Aleisa; Rachid Sougrat; Jasmeen S. Merzaban; Niveen M. Khashab

Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer cell coated zeolitic imidazolate frameworks (ZIFs) for targeted and cell-specific delivery of this genome editing machinery. Coating ZIF-8 that is encapsulating CRISPR/Cas9 (CC-ZIF) with a cancer cell membrane resulted in the uniformly covered C3-ZIF(cell membrane type). Incubation of C3-ZIFMCF with MCF-7, HeLa, HDFn, and aTC cell lines showed the highest uptake by MCF-7 cells and negligible uptake by the healthy cells (i.e., HDFn and aTC). As to genome editing, a 3-fold repression in the EGFP expression was observed when MCF-7 were transfected with C3-ZIFMCF compared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C3-ZIFHELA. In vivo testing confirmed the selectivity of C3-ZIFMCF to accumulate in MCF-7 tumor cells. This supports the ability of this biomimetic approach to match the needs of cell-specific targeting, which is unquestionably the most critical step in the future translation of genome editing technologies.
更新日期:2020-01-17

 

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