ArticleMolecular therapy. Methods & clinical development2022
Structural basis for the neurotropic AAV9 and the engineered AAVPHP.eB recognition with cellular receptors.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Controllable gene delivery via masked adeno-associated viral vectors.Nature materials · 2026Article
- AAV2 bypasses direct endosomal escape by using AAVR to access the trans-Golgi network en route to the nucleus.Journal of virology · 2026Article
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- Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
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- AAV9-Mimetic Peptides and Electroporation Synergistically Enhance Nanoparticle Transport through the Blood-Brain Barrier.ACS biomaterials science & engineering · 2026Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Plasmonic Nanopore Sensing to Probe the DNA Loading Status of Adeno-Associated Viruses.Chemosensors (Basel, Switzerland) · 2025Article
- Structural studies of Parvoviridae capsid assembly and evolution: implications for novel AAV vector design.Frontiers in artificial intelligence · 2025Review
- Quantification of full and empty particles of adeno-associated virus vectors via a novel dual fluorescence-linked immunosorbent assay.Molecular therapy. Methods & clinical development · 2024Article
- An engineered AAV targeting integrin alpha V beta 6 presents improved myotropism across species.Nature communications · 2024Article
- Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.Nature communications · 2024Article
- Unlocking precision gene therapy: harnessing AAV tropism with nanobody swapping at capsid hotspots.NAR molecular medicine · 2024Article
- Fast, accurate ranking of engineered proteins by target-binding propensity using structure modeling.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Unlocking Precision Gene Therapy: Harnessing AAV Tropism with Nanobody Swapping at Capsid Hotspots.bioRxiv : the preprint server for biology · 2024Article
- Review
- Structural basis of the recognition of adeno-associated virus by the neurological system-related receptor carbonic anhydrase IV.PLoS pathogens · 2024Article
- Engineering a highly durable adeno-associated virus receptor for analytical applications.Molecular therapy. Methods & clinical development · 2023Article
- Characterization and biodistribution of under-employed gene therapy vector AAV7.Journal of virology · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clade F adeno-associated virus (AAV) 9 has been utilized as therapeutic gene delivery vector, and it is capable of crossing blood brain barrier (BBB). Recently, an AAV9-based engineering serotype AAVPHP.eB with enhanced BBB crossing ability further expanded clade F AAVs' usages in the murine central nervous system (CNS) gene delivery. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of the AAVPHP.eB and its parental serotype AAV9 in native form or in complex with their essential receptor AAV receptor (AAVR). These structures reveal the molecular details of their AAVR recognition, where the polycystic kidney disease repeat domain 2 (PKD2) of AAVR interacts with AAV9 and AAVPHP.eB virions at the 3-fold protrusions and the raised capsid regions between the 2- and 5-fold axes, termed the 2/5-fold wall. The interacting patterns of AAVR to AAV9 and AAVPHP.eB are similar to what was observed in AAV1/AAV2-AAVR complexes. Moreover, we found that the AAVPHP.eB variable region VIII (VR-VIII) may independently facilitate the new receptor recognition responsible for enhanced CNS transduction. Our study provides insights into the recognition principles of multiple receptors for engineered AAVPHP.eB and parental serotype AAV9, and further reveal the potential molecular basis underlying their different tropisms.
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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.