ArticleGene therapy2018
Rationally designed AAV2 and AAVrh8R capsids provide improved transduction in the retina and brain.
Article in Gene therapy, 2018. 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, 34 citations in OpenAlex.
- Focused ultrasound expands intra-CSF AAV delivery to deep brain regions in rats and non-human primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Interrogating the dependency of AAV capsids on AAVR for retinal transduction.Molecular therapy. Advances · 2026Article
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy.Frontiers in neurology · 2025Review
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations.Molecular therapy. Nucleic acids · 2024Article
- An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.Nature communications · 2024Article
- Improved gene therapy for MFRP deficiency-mediated retinal degeneration by knocking down endogenous bicistronicMolecular therapy. Nucleic acids · 2023Article
- The engineered AAV2-HBKO promotes non-invasive gene delivery to large brain regions beyond ultrasound targeted sites.Molecular therapy. Methods & clinical development · 2022Article
- Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.Journal of personalized medicine · 2022Review
- Molecular Signature of Astrocytes for Gene Delivery by the Synthetic Adeno-Associated Viral Vector rAAV9P1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann-Pick disease type C1 mice.Life science alliance · 2021Article
- A 2020 vision of ocular gene therapy.Gene therapy · 2021Article
- Effects of Altering HSPG Binding and Capsid Hydrophilicity on Retinal Transduction by AAV.Journal of virology · 2021Article
- [Expression pattern of different serotypes of adeno-associated viral vectors in mouse retina].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2020Article
- Peripapillary Intravitreal Injection Improves AAV-Mediated Retinal Transduction.Molecular therapy. Methods & clinical development · 2020Article
- Attenuation of Heparan Sulfate Proteoglycan Binding EnhancesMolecular therapy. Methods & clinical development · 2020Article
- Novel AAV44.9-Based Vectors Display Exceptional Characteristics for Retinal Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Intra-striatal AAV2.retro administration leads to extensive retrograde transport in the rhesus macaque brain: implications for disease modeling and therapeutic development.Scientific reports · 2020Article
- Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges.Neuroscience letters · 2019Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO. In contrast to parental AAV2, the AAV2-HBKO vector displayed low-transduction activity following intravitreal delivery to the mouse eye; however, following its subretinal delivery, AAV2-HBKO resulted in significantly greater photoreceptor transduction. Intrastriatal delivery of AAV2-HBKO to mice facilitated widespread striatal and cortical expression, in contrast to the restricted transduction pattern of the parental AAV2 vector. Furthermore, we found that altering the surface charge on the AAVrh8R capsid by modifying the number of arginine residues on the capsid surface had a profound impact on subretinal transduction. The data further validate the potential of capsid engineering to improve AAV gene therapy vectors for clinical applications.
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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.