Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework
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.
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Zeolitic imidazole frameworks and graphene oxide-PEG-polyethylenimine have been investigated to facilitate endosomal evasion.
“Some materials, such as zeolitic imidazole frameworks (ZIFs) [229] and graphene oxide (GO)-PEG-polyethylenimine (PEI) [230] have been investigated to facilitate endosomal evasion.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [229]
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- Authors
- Alsaiari, S. K., Patil, S., Alyami, M., Alamoudi, K. O., Aleisa, F. A., Merzaban, J. S., Li, M., & Khashab, N. M.
- Affiliations
- King Abdullah University of Science and Technology (SA)
- Corresponding author
- Khashab, Niveen M.
- ORCID
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-12-27
- Volume
- 140
- Issue
- 1
- Pages
- 143-146
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2778319634
- Cited by
- 517
- References
- 25
- Citations by year
- 2026: 32 · 2025: 47 · 2024: 60 · 2023: 70 · 2022: 71 · 2021: 90 · 2020: 66 · 2019: 55 · 2018: 26
- FWCI
- 16.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- CRISPR/Cas9, zeolitic imidazolate frameworks, ZIF-8, endosomal escape, gene delivery, genome editing, single guide RNA, nanocarriers, biocompatibility
- MeSH terms
- Gene Editing, Animals, Cricetulus, Imidazoles, Particle Size, Endosomes, CHO Cells, Zeolites, Nanoparticles, CRISPR-Cas Systems
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