Coordination-based self-assembled capsules (SACs) for protein, CRISPR-Cas9, DNA and RNA delivery.

Biologics, such as functional proteins and nucleic acids, have recently dominated the drug market and comprise seven out of the top 10 best-selling drugs. Biologics are usually polar, heat sensitive, membrane impermeable and subject to enzymatic degradation and thus require systemic routes of administration and delivery. Coordination-based delivery vehicles, which include nanosized extended metal-organic frameworks (nMOFs) and discrete coordination cages, have gained a lot of attention because of their remarkable biocompatibility, in vivo stability, on-demand biodegradability, high encapsulation efficiency, easy surface modification and moderate synthetic conditions. Consequently, these systems have been extensively utilized as carriers of biomacromolecules for biomedical applications. This review summarizes the recent applications of nMOFs and coordination cages for protein, CRISPR-Cas9, DNA and RNA delivery. We also highlight the progress and challenges of coordination-based platforms as a promising approach towards clinical biomacromolecule delivery and discuss integral future research directions and applications.

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-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.