ArticleGene therapy2021
Highly efficient neuronal gene knockout in vivo by CRISPR-Cas9 via neonatal intracerebroventricular injection of AAV in mice.
Article in Gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Noninvasive Focal Gene Delivery into the Cerebellum of Non-Human Primates using Focused Ultrasound.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Early postnatal expression mitigates immune responses to Cas9 in the murine central nervous system.Molecular therapy. Methods & clinical development · 2025Article
- Article
- A versatile immunomodulated nanoCRISPR converter augments the susceptibility and visibility of tumors to the immune system.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.iScience · 2025Review
- Allele-Specific Editing of a Dominant SCN8A Epilepsy Variant Protects against Seizures and Lethality in a Murine Model.Annals of neurology · 2024Article
- Techniques for investigating lncRNA transcript functions in neurodevelopment.Molecular psychiatry · 2024Review
- Acoustically targeted noninvasive gene therapy in large brain volumes.Gene therapy · 2024Article
- Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.International journal of molecular sciences · 2023Review
- Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases.Biomedicines · 2023Review
- rAAV-PHP.B escapes the mouse eye and causes lethality whereas rAAV9 can transduce aniridic corneal limbal stem cells without lethality.Gene therapy · 2023Article
- Removal of evolutionarily conserved functional MYC domains in a tilapia cell line using a vector-based CRISPR/Cas9 system.Scientific reports · 2023Article
- Inhibition of LAR attenuates neuroinflammation through RhoA/IRS-1/Akt signaling pathway after intracerebral hemorrhage in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Genetic modulation of thePNAS nexus · 2023Article
- The potential of gene editing for Huntington's disease.Trends in neurosciences · 2023Review
- CRISPR/Cas9 for hepatitis B virus infection treatment.Immunity, inflammation and disease · 2023Review
- Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins.Biomaterials · 2023Article
- Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.Diagnostics (Basel, Switzerland) · 2023Review
- Revisiting the outcome of adult wild-typeBrain communications · 2023Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR-Cas systems have emerged as a powerful tool to generate genetic models for studying normal and diseased central nervous system (CNS). Targeted gene disruption at specific loci has been demonstrated successfully in non-dividing neurons. Despite its simplicity, high specificity and low cost, the efficiency of CRISPR-mediated knockout in vivo can be substantially impacted by many parameters. Here, we used CRISPR-Cas9 to disrupt the neuronal-specific gene, NeuN, and optimized key parameters to achieve effective gene knockout broadly in the CNS in postnatal mice. Three cell lines and two primary neuron cultures were used to validate the disruption of NeuN by single-guide RNAs (sgRNA) harboring distinct spacers and scaffold sequences. This triage identified an optimal sgRNA design with the highest NeuN disruption in in vitro and in vivo systems. To enhance CRISPR efficiency, AAV-PHP.B, a vector with superior neuronal transduction, was used to deliver this sgRNA in Cas9 mice via neonatal intracerebroventricular (ICV) injection. This approach resulted in 99.4% biallelic indels rate in the transduced cells, leading to greater than 70% reduction of total NeuN proteins in the cortex, hippocampus and spinal cord. This work contributes to the optimization of CRISPR-mediated knockout and will be beneficial for fundamental and preclinical research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.