ArticleMolecular therapy. Nucleic acids2019
Targeted Transgene Activation in the Brain Tissue by Systemic Delivery of Engineered AAV1 Expressing CRISPRa.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Restoring the Balance: CRISPRa-Driven β-Tubulin Compensation as a Strategy for Tubulinopathy Treatment.International journal of molecular sciences · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Therapeutic in vivo genome editing: innovations and challenges in rAAV vector-based CRISPR delivery.Gene therapy · 2026Review
- CRISPR activation to repair electrocardiogram abnormalities caused by a FLNC truncating variant in mice.European heart journal · 2025Article
- Epigenome Engineering Using dCas Systems for Biomedical Applications and Biotechnology: Current Achievements, Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Viral and nonviral nanocarriers forNano research · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Discovery of Diverse CRISPR-Cas Systems and Expansion of the Genome Engineering Toolbox.Biochemistry · 2023Review
- Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases.Biomedicines · 2023Review
- Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.Nature communications · 2023Article
- Multi-faceted CRISPR/Cas technological innovation aspects in the framework of 3P medicine.The EPMA journal · 2023Review
- Gene Modulation with CRISPR-based Tools in Human iPSC-Cardiomyocytes.Stem cell reviews and reports · 2023Review
- Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.bioRxiv : the preprint server for biology · 2023Article
- PAM-flexible dual base editor-mediated random mutagenesis and self-activation strategies to improve CRISPRa potency.Molecular therapy. Methods & clinical development · 2022Article
- Dead Cas(t) light on new life: CRISPRa-mediated reprogramming of somatic cells into neurons.Cellular and molecular life sciences : CMLS · 2022Review
- Heterogeneity of human corneal endothelium implicates lncRNAMolecular therapy. Nucleic acids · 2022Article
- Genetic correction strategies for Duchenne Muscular Dystrophy and their impact on the heart.Progress in pediatric cardiology · 2021Article
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
- Tissue-specific activation of gene expression by the Synergistic Activation Mediator (SAM) CRISPRa system in mice.Nature communications · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted transcriptional modulation in the central nervous system (CNS) can be achieved by adeno-associated virus (AAV) delivery of CRISPR activation (CRISPRa) and interference (CRISPRi) transgenes. To enable AAV packaging, we constructed minimal CRISPRa and CRISPRi transgenes by fusing catalytically inactive Staphylococcus aureus Cas9 (dSaCas9) to the transcriptional activator (VP64 and VP160) and repressor (KRAB and SID4X) domains along with truncated regulatory elements. We then evaluated the performance of these constructs in two reporter assays (bioluminescent and fluorescent), five endogenous genes (Camk2a, Mycn, Nrf2, Keap1, and PDGFRA), and two cell lines (neuro-2a [N2a] and U87) by targeting the promoter and/or enhancer regions. To enable systemic delivery of AAVs to the CNS, we have also generated an AAV1-PHP.B by inserting a 7-mer PHP.B peptide on AAV1 capsid. We showed that AAV1-PHP.B can efficiently cross the blood-brain barrier (BBB) and be taken up by the brain tissue upon lateral tail vein injection in mice. Importantly, a single-dose intravenous administration of AAV1-PHP.B expressing CRISPRa was shown to achieve targeted transgene activation in the mouse brain. This proof-of-concept study will contribute to the development of a non-invasive, specific and potent AAV-CRISPR system for correcting transcriptional misregulation in broad brain areas and multiple neuroanatomical structures.
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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.