Direct cytosolic delivery of CRISPR/Cas9-ribonucleoprotein for efficient gene editing
Open accessAbstract
Genome editing through the delivery of CRISPR/Cas9-ribonucleoprotein (Cas9-RNP) reduces unwanted gene targeting and avoids integrational mutagenesis that can occur through gene delivery strategies. Direct and efficient delivery of Cas9-RNP into the cytosol followed by translocation to the nucleus remains a challenge. Here, we report a remarkably highly efficient (∼90%) direct cytoplasmic/nuclear delivery of Cas9 protein complexed with a guide RNA (sgRNA) through the coengineering of Cas9 protein and carrier nanoparticles. This construct provides effective (∼30%) gene editing efficiency and opens up opportunities in studying genome dynamics.
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Cationic arginine gold nanoparticles were prepared to directly deliver Cas9 RNPs into the cellular cytoplasm without endocytosis.
“Furthermore, Mout et al. prepared cationic arginine gold nanoparticles (ArgNPs) to directly deliver Cas9 RNPs into the cellular cytoplasm without endocytosis.[231]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [231]
Mout et al.'s arginine-modified gold nanoparticle nanoplatform achieved effective gene editing efficiency up to 30% in HeLa, HEK-293T and Raw 264.7 cell lines.
“With this approach, they edited AAVS1 gene and PTEN gene and achieved effective gene editing efficiency up to 30% in HeLa, HEK-293T and Raw 264.7 cell lines (Fig. 2A) [97].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [97]
First obstacle: effective encapsulation of editing tools in delivery vectors is hindered by large size and different charge properties of Cas9 protein, mRNA and donor DNA.
“The first obstacle is effective encapsulation of the editing tools in delivery vectors due to the large size and different charge properties of Cas9 protein, mRNA and donor DNA.”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [97]
Native Cas9 protein is positively charged, while conventional proteins are negatively charged.
“Meanwhile, native Cas9 protein is positively charged, while the conventional proteins are negatively charged [88, 97, 103, 139].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [97]
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- Authors
- Mout, R., Ray, M., Yesilbag Tonga, G., Lee, Y.-W., Tay, T., Sasaki, K., & Rotello, V. M.
- Affiliations
- University of Massachusetts Amherst (US)
- Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, United States
- Corresponding author
- Rotello, Vincent M.
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-01-31
- Volume
- 11
- Issue
- 3
- Pages
- 2452-2458
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC5848212
- OpenAlex
- W2581151188
- Cited by
- 579
- References
- 29
- Citations by year
- 2026: 36 · 2025: 62 · 2024: 56 · 2023: 50 · 2022: 76 · 2021: 74 · 2020: 79 · 2019: 67 · 2018: 51 · 2017: 26
- FWCI
- 24.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Division of Chemistry (CHE-1307021)
- National Institute of General Medical Sciences (GM077173)
- Office of Technology Commercialization and Ventures, University of Massachusetts Amherst
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- CRISPR/Cas9 ribonucleoprotein, cytosolic delivery, nuclear translocation, guide RNA, nanocarriers, genome editing efficiency, genome dynamics
- MeSH terms
- Gene Editing, Cytosol, Ribonucleoproteins, Protein Engineering, Gene Transfer Techniques, CRISPR-Cas Systems
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