ArticleMolecular therapy. Nucleic acids2017
Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
53 citing papers in PubMed, 70 citations in OpenAlex.
- Recent advancements in improving cross-species applicability of bioengineered AAV capsids.Gene therapy · 2026Review
- Construct optimization for AAV-mediated human α-syn overexpression, and validation across research settings: Development of a shared tool for the research community.Journal of Parkinson's disease · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- Effects of chemogenetic inhibition of serotonergic raphe-striatal neurons on L-DOPA-induced behaviors and neurochemistry in a rat model of Parkinson's disease.Acta neuropathologica communications · 2026Article
- Astrocytic noncanonical WNT5B signaling modulates extracellular matrix remodeling and neuropathology in Huntington's disease.Signal transduction and targeted therapy · 2026Article
- Genetically Encoded SpyTag Enables Modular AAV Retargeting via SpyCatcher-Fused Ligands for Targeted Gene Delivery.ACS synthetic biology · 2026Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- Disease-modifying, multidimensional efficacy of putaminal CaMolecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advancing age and sex modulate antidyskinetic efficacy of striatal CaNeurobiology of aging · 2025Article
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Review
- Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024Review
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Identification and validation of novel engineered AAV capsid variants targeting human glia.Frontiers in neuroscience · 2024Article
- Review
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- CRISPR/Cas9 Genome Editing for Tissue-Specific In Vivo Targeting: Nanomaterials and Translational Perspective.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) is the most common vector for clinical gene therapy of the CNS. This popularity originates from a high safety record and the longevity of transgene expression in neurons. Nevertheless, clinical efficacy for CNS indications is lacking, and one reason for this is the relatively limited spread and transduction efficacy in large regions of the human brain. Using rationally designed modifications of the capsid, novel AAV capsids have been generated that improve intracellular processing and result in increased transgene expression. Here, we sought to improve AAV-mediated neuronal transduction to minimize the existing limitations of CNS gene therapy. We investigated the efficacy of CNS transduction using a variety of tyrosine and threonine capsid mutants based on AAV2, AAV5, and AAV8 capsids, as well as AAV2 mutants incapable of binding heparan sulfate (HS). We found that mutating several tyrosine residues on the AAV2 capsid significantly enhanced neuronal transduction in the striatum and hippocampus, and the ablation of HS binding also increased the volumetric spread of the vector. Interestingly, the analogous tyrosine substitutions on AAV5 and AAV8 capsids did not improve the efficacy of these serotypes. Our results demonstrate that the efficacy of CNS gene transfer can be significantly improved with minor changes to the AAV capsid and that the effect is serotype specific.
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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.