biostudies-literatureHsi-Bell JNational Institute of Nursing ResearchNational Institute of General Medical SciencesNational Science Foundation101629https://www.ebi.ac.uk/biostudies/studies/S-EPMC12682079biostudies-literatureUnknown33(4)Over the past ∼25 years, structural studies of adeno-associated virus (AAV) capsids have greatly aided our understanding of the biology of these single-stranded DNA viruses and provided insights into their utilization as gene therapy vectors for the treatment of various human diseases. Recent advances in cryo-electron microscopy have yielded a library of currently ∼150 high-resolution AAV capsid structures, with more than 50% determined in the last 5 years alone. Comparative analyses of capsids from primate and nonprimate origins have revealed both conserved architectural elements, such as the canonical jelly-roll fold, and critical surface variations that affect receptor interaction, antibody recognition, and intracellular trafficking. These structures, as well as those in complex with glMolecular therapy. Methods & clinical developmentThe amazing AAV capsids: Into the structure-verse.PMC12682079GM082946DGE-2236414Mietzsch MHsi-Bell JMcKenna RfalseThe amazing AAV capsids: Into the structure-verse.Over the past ∼25 years, structural studies of adeno-associated virus (AAV) capsids have greatly aided our understanding of the biology of these single-stranded DNA viruses and provided insights into their utilization as gene therapy vectors for the treatment of various human diseases. Recent advances in cryo-electron microscopy have yielded a library of currently ∼150 high-resolution AAV capsid structures, with more than 50% determined in the last 5 years alone. Comparative analyses of capsids from primate and nonprimate origins have revealed both conserved architectural elements, such as the canonical jelly-roll fold, and critical surface variations that affect receptor interaction, antibody recognition, and intracellular trafficking. These structures, as well as those in complex with gl2025-01-01T00:00:00Z2025 Dec2026-06-06T00:29:53.925Z2026-05-24T03:11:40.681ZS-EPMC126820794136229010.1016/j.omtm.2025.101629