The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours
Open accessAbstract
Technologies that can safely edit genes in the brains of adult animals may revolutionize the treatment of neurological diseases and the understanding of brain function. Here, we demonstrate that intracranial injection of CRISPR-Gold, a nonviral delivery vehicle for the CRISPR-Cas9 ribonucleoprotein, can edit genes in the brains of adult mice in multiple mouse models. CRISPR-Gold can deliver both Cas9 and Cpf1 ribonucleoproteins, and can edit all of the major cell types in the brain, including neurons, astrocytes and microglia, with undetectable levels of toxicity at the doses used. We also show that CRISPR-Gold designed to target the metabotropic glutamate receptor 5 (mGluR5) gene can efficiently reduce local mGluR5 levels in the striatum after an intracranial injection. The effect can also rescue mice from the exaggerated repetitive behaviours caused by fragile X syndrome, a common single-gene form of autism spectrum disorders. CRISPR-Gold may significantly accelerate the development of brain-targeted therapeutics and enable the rapid development of focal brain-knockout animal models.
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“Lee et al. (2018) further demonstrated that CRISPR-Gold which contains gold nanoparticles and Cas9 RNPs was able to successfully edit target gene and rescue increased repetitive behaviors in a mouse model for fragile X syndrome, a neurodevelopmental disorder (33). This was achieved by injecting directly into the striatum (33).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [33]
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“Through intracranial injection of 2 μL of CRISPR-Gold, both the mRNA and protein levels of mGluR5 decreased 40–50% in FXS mice.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [44]
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“Furthermore, the treated FXS mice significantly resumed exaggerated repetitive behaviors after three weeks.[44]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [44]
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Metadata
- Authors
- Lee, B., Lee, K., Panda, S., Gonzales-Rojas, R., Chong, A., Bugay, V., Park, H. M., Brenner, R., Murthy, N., & Lee, H. Y.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of California, Berkeley (US)
- Corresponding author
- Murthy, Niren
- Lee, Hye Young
- Venue
- Nature Biomedical Engineering
- Published
- 2018-06-25
- Volume
- 2
- Issue
- 7
- Pages
- 497-507
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC6544395
- OpenAlex
- W2810249184
- Cited by
- 361
- References
- 54
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 36 · 2023: 42 · 2022: 58 · 2021: 56 · 2020: 66 · 2019: 38 · 2018: 15
- FWCI
- 16.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI117064)
- National Institute of Biomedical Imaging and Bioengineering (R01EB023776, R01EB020008)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- CRISPR/Cas9 delivery, non-viral gene delivery, intracranial injection, fragile X syndrome, repetitive behavior, metabotropic glutamate receptor 5, mGluR5, CRISPR/Cas12a, striatum, autism spectrum disorder, astrocytes, microglia, neurons
- MeSH terms
- Animals, Behavior, Animal, Brain, Corpus Striatum, Disease Models, Animal, Fragile X Syndrome, Gold, Humans, Mice, Inbred C57BL, Neurons, Mice, Knockout, Patch-Clamp Techniques, Thy-1 Antigens, Mice, Fragile X Messenger Ribonucleoprotein 1, Nanoparticles, HEK293 Cells, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, Receptor, Metabotropic Glutamate 5
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