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Fast and Efficient CRISPR/Cas9 Genome Editing In Vivo Enabled by Bioreducible Lipid and Messenger RNA Nanoparticles
Open accessAbstract
A main challenge to broaden the biomedical application of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9) genome editing technique is the delivery of Cas9 nuclease and single‐guide RNA (sgRNA) into the specific cell and organ. An effective and very fast CRISPR/Cas9 genome editing in vitro and in vivo enabled by bioreducible lipid/Cas9 messenger RNA (mRNA) nanoparticle is reported. BAMEA‐O16B, a lipid nanoparticle integrated with disulfide bonds, can efficiently deliver Cas9 mRNA and sgRNA into cells while releasing RNA in response to the reductive intracellular environment for genome editing as fast as 24 h post mRNA delivery. It is demonstrated that the simultaneous delivery of Cas9 mRNA and sgRNA using BAMEA‐O16B knocks out green fluorescent protein (GFP) expression of human embryonic kidney cells with efficiency up to 90%. Moreover, the intravenous injection of BAMEA‐O16B/Cas9 mRNA/sgRNA nanoparticle effectively accumulates in hepatocytes, and knocks down proprotein convertase subtilisin/kexin type 9 level in mouse serum down to 20% of nontreatment. The leading lipid nanoparticle, BAMEA‐O16B, represents one of the most efficient CRISPR/Cas9 delivery nanocarriers reported so far, and it can broaden the therapeutic promise of mRNA and CRISPR/Cas9 technique further.
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“Gene-editing components can be delivered by lipid nanoparticle–mRNA formulations to treat genetic diseases, including HTI92,238, hypercholesterolaemia81,96,105,239, lipoprotein metabolism disorders85 and transthyretin amyloidosis239,240, which has been demonstrated in preclinical studies.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [81]
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The Application of the CRISPR/Cas9 System in the Treatment of Hepatitis B Liver Cancer
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BackgroundA zwitterionic polymer-inspired material mediated efficient CRISPR-Cas9 gene editing
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BackgroundLipids and lipid derivatives for delivery of the CRISPR/Cas9 system
Madhi, Z. S., Shallan, M. A., Almaamuri, A. M., Alhussainy, A. A., AL-Salih, S. S. H., Raheem, A. K., Alwan, H. J., & Jalil, A. T. (2022) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2022.103948 · Cited by 8
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Treating Cardiovascular Disease with Liver Genome Engineering
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A Coordinative Dendrimer Achieves Excellent Efficiency in Cytosolic Protein and Peptide Delivery
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A comprehensive review on lipid-based nanoparticles via nose to brain targeting as a novel approach
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Metadata
- Authors
- Liu, J., Chang, J., Jiang, Y., Meng, X., Sun, T., Mao, L., Xu, Q., & Wang, M.
- Affiliations
- Chinese Academy of Sciences (CN)
- Jilin University (CN)
- Tufts University (US)
- Corresponding author
- Xu, Qiaobing
- Wang, Ming
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2019-06-19
- Volume
- 31
- Issue
- 33
- Pages
- e1902575-e1902575
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- PMC
- PMC6732788
- OpenAlex
- W2950978761
- Cited by
- 373
- References
- 33
- Citations by year
- 2026: 33 · 2025: 52 · 2024: 53 · 2023: 55 · 2022: 74 · 2021: 53 · 2020: 45 · 2019: 8
- FWCI
- 14.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Basic Research Program of China (2017YFA0208100, 2016YFA0200104)
- National Natural Science Foundation of China (21778056, 21790390, 21790391, 21621062, 21435007)
- National Science Foundation (UG3 TR002636‐01, NIH R21 EB024041)
- 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 genome editing, lipid nanoparticles, hepatocyte targeting, in vivo gene editing
- MeSH terms
- Proprotein Convertase 9, Gene Editing, CRISPR-Associated Protein 9, RNA, Guide, CRISPR-Cas Systems, Animals, Biological Transport, Humans, Lipids, Oxidation-Reduction, RNA, Messenger, RNA, Guide, Kinetoplastida, Gene Transfer Techniques, Cell Line, Tumor, Green Fluorescent Proteins, Mice, Nanoparticles, Gene Knockdown Techniques
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