Effective and cell-type specific delivery of CRISPR/Cas9 gene editing elements remains a challenge. 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-ZIFs) with cancer cell membrane resulted in the uniformly covered C3-ZIFs. Incubation of C3-ZIFsMCFwith MCF-7, HeLa, HDFn and aTC cell lines showed negligible uptake in the healthy HDFn and aTC cells, whereas MCF-7 showed the highest uptake. As to genome editing, a 3-fold repression in the EGFP expression was observed when MCF-7 were transfected with C3-ZIFsMCFcompared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C3-ZIFsHELA.This supports the ability of this biomimetic approach to match the needs for cell-specific targeting which is unquestionably the most critical step in the translation of genome editing technologies.

Cell-type-specific CRISPR/Cas9 delivery by biomimetic metal organic frameworks

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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