ArticleMolecular therapy. Methods & clinical development2021
High throughput screening of novel AAV capsids identifies variants for transduction of adult NSCs within the subventricular zone.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Nrsn1-Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic-phase Recovery After Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted gene transfer into developmentally defined cell populations of the primate brain.Cell reports · 2026Article
- DMTF1 up-regulation rescues proliferation defect of telomere dysfunctional neural stem cells via the SWI/SNF-E2F axis.Science advances · 2026Article
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cross-species comparison reveals therapeutic vulnerabilities halting glioblastoma progression.Nature communications · 2025Article
- Mapping administration route-dependent transduction profiles of commonly used AAV variants in mice by barcode amplicon sequencing.Molecular therapy. Methods & clinical development · 2025Article
- The Pathogenesis and Prevention Strategies of Radiation-Induced Brain Injury.Cancer management and research · 2025Review
- Deficiency of FABP7 Triggers Premature Neural Differentiation in Idiopathic Normocephalic Autism Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Nucleic acid-based drugs for patients with solid tumours.Nature reviews. Clinical oncology · 2024Review
- rAAV2-Mediated Restoration of GALC in Neural Stem Cells from Krabbe Patient-Derived iPSCs.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle.EMBO molecular medicine · 2023Article
- Massively Parallel Reporter Assays for High-Throughput In Vivo Analysis of Cis-Regulatory Elements.Journal of cardiovascular development and disease · 2023Review
- Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.Science advances · 2022Article
- High-throughput scNMT protocol for multiomics profiling of single cells from mouse brain and pancreatic organoids.STAR protocols · 2022Article
- Fantastic AAV Gene Therapy Vectors and How to Find Them-Random Diversification, Rational Design and Machine Learning.Pathogens (Basel, Switzerland) · 2022Review
- Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening.Scientific reports · 2022Article
- Adeno-Associated Viruses for Modeling Neurological Diseases in Animals: Achievements and Prospects.Biomedicines · 2022Review
- Delivery of CRISPR-Cas9 system for screening and editing RNA binding proteins in cancer.Advanced drug delivery reviews · 2022Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adult mammalian brain entails a reservoir of neural stem cells (NSCs) generating glial cells and neurons. However, NSCs become increasingly quiescent with age, which hampers their regenerative capacity. New means are therefore required to genetically modify adult NSCs for re-enabling endogenous brain repair. Recombinant adeno-associated viruses (AAVs) are ideal gene-therapy vectors due to an excellent safety profile and high transduction efficiency. We thus conducted a high-throughput screening of 177 intraventricularly injected barcoded AAV variants profiled by RNA sequencing. Quantification of barcoded AAV mRNAs identified two synthetic capsids, peptide-modified derivative of wild-type AAV9 (AAV9_A2) and peptide-modified derivative of wild-type AAV1 (AAV1_P5), both of which transduce active and quiescent NSCs. Further optimization of AAV1_P5 by judicious selection of the promoter and dose of injected viral genomes enabled labeling of 30%-60% of the NSC compartment, which was validated by fluorescence-activated cell sorting (FACS) analyses and single-cell RNA sequencing. Importantly, transduced NSCs readily produced neurons. The present study identifies AAV variants with a high regional tropism toward the ventricular-subventricular zone (v-SVZ) with high efficiency in targeting adult NSCs, thereby paving the way for preclinical testing of regenerative gene therapy.
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