Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework

by ALsaiari, Shahad K., Patil, Sachin, Alyami, Mram, Alamoudi, Kholod O., Aleisa, Fajr A., Merzaban, Jasmeen S., Li, Mo, Khashab, Niveen M.
Year: 2018

Bibliography

Alsaiari, Shahad K.; Patil, Sachin; Alyami, Mram; Alamoudi, Kholod O.; Aleisa, Fajr A.; Merzaban, Jasmeen S.; Li, Mo; Khashab, Niveen M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. Journal of the American Chemical Society (2018), 140(1), 143-146

Abstract

​CRISPR/Cas9 is a combined protein (Cas9) and an engineered single guide RNA (sgRNA) genome editing platform that offers revolutionary solutions to genetic diseases. It has, however, a double delivery problem owning to the large protein size and the highly charged RNA component. In this work, we report the first example of CRISPR/Cas9 encapsulated by nanoscale zeolitic imidazole frameworks (ZIFs) with a loading efficiency of 17% and enhanced endosomal escape promoted by the protonated imidazole moieties. The gene editing potential of CRISPR/Cas9 encapsulated by ZIF-8 (CC-ZIFs) is further verified by knocking down the gene expression of green fluorescent protein by 37% over 4 days. The nanoscale CC-ZIFs are biocompatible and easily scaled-up offering excellent loading capacity and controlled codelivery of intact Cas9 protein and sgRNA.

Pub_2018_EED

Keywords

CRISPR Delivery Protein Delivery ZIFs