Cell-type-specific CRISPR/Cas9 delivery by Biomimetic Metal Organic Frameworks

by Mram Z. Alyami, Shahad K. Alsaiari, Yanyan Li, Somayah S. Qutub, Fajr A. Aleisa, Rachid Sougrat, Jasmeen S. Merzaban, Niveen M. Khashab
Year: 2020

Bibliography

Mram Z. Alyami, Shahad K. Alsaiari, Yanyan Li, Somayah S. Qutub, Fajr A. Aleisa, Rachid Sougrat, Jasmeen S. Merzaban, and Niveen M. Khashab; Cell-type-specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks; J. Am. Chem. Soc., 2020, 142, 1715−1720

Abstract

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 cellspecific 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 cellspecific targeting, which is unquestionably the most critical step in the future translation of genome editing technologies.

Keywords

Biomimetic MOFs MOFs Cancer cells