Cell-Type-Specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks
AuthorsAlyami, Mram Z.
Alsaiari, Shahad K.
Qutub, Somayah S.
Aleisa, Fajr A
Khashab, Niveen M.
KAUST DepartmentAdvanced Membranes and Porous Materials Research Center
Biological and Environmental Sciences and Engineering (BESE) Division
Chemical Science Program
Physical Science and Engineering (PSE) Division
Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Smart Hybrid Materials (SHMs) lab
Online Publication Date2020-01-14
Print Publication Date2020-01-29
Embargo End Date2021-01-14
Permanent link to this recordhttp://hdl.handle.net/10754/661072
MetadataShow full item record
AbstractEffective 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.
CitationAlyami, M. Z., Alsaiari, S. K., Li, Y., Qutub, S. S., Aleisa, F. A., Sougrat, R., … Khashab, N. M. (2020). Cell-Type-Specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks. Journal of the American Chemical Society. doi:10.1021/jacs.9b11638
SponsorsThis work was supported by King Abdullah University of Science and Technology (KAUST).
PublisherAmerican Chemical Society (ACS)