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 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-ZIF_MCF 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-ZIF_MCF compared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C³-ZIF_HELA. In vivo testing confirmed the selectivity of C³-ZIF_MCF 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.