Cell-Type-Specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks

Effective and cell-type specific delivery of CRISPR/Cas9 gene editing elements remains a chal-lenging open problem. Here we report the devel-opment of biomimetic cancer cell coated zeolitic imidazolate frameworks (ZIFs) for targeted and cell-specific delivery of this genome editing ma-chinery. Coating ZIF-8 that is encapsulating CRISPR/Cas9 (CC-ZIF) with 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 ob-served when MCF-7 were transfected with C3-ZIFMCF compared to 1-fold repression in the EGFP expres-sion 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 targeti...