@article{Xu:2026:10.1016/j.celrep.2026.117044,
author = {Xu, V and McInnes, A and Wake, M and Acebrón-García-de-Eulate, M and Barritt, JD and Bubeck, D and Rouse, SL},
doi = {10.1016/j.celrep.2026.117044},
journal = {Cell Reports},
title = {Structural basis for Rep-mediated adeno-associated virus packaging},
url = {http://dx.doi.org/10.1016/j.celrep.2026.117044},
volume = {45},
year = {2026}
}

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TY  - JOUR
AB  - Adeno-associated viruses (AAVs) are parvoviruses utilized as gene therapy vectors. However, the AAV packaging mechanism is unresolved at the molecular level, creating a bottleneck for vector manufacturing, safety, and efficacy. Here, cryo-EM structures of the Rep helicase packaging motor in complex with the packaging marker DNA (ITR) and the Rep-AAV8 capsid complex are presented. Rep-ITR complexes reveal dynamic oligomeric states on the DNA, elucidating the strand separation mechanism coupled to its ATPase cycle. We observe Rep preferentially bound to empty capsids, with a binding interface likely conserved across the virus family. This complex also unveils a cryptic capsid ATP-binding site which, alongside Rep binding, triggers structural rearrangements priming the capsid for packaging. Collectively, these findings advance the understanding of Rep-mediated packaging, with significant implications for parvovirus virology and viral vector design.
AU  - Xu,V
AU  - McInnes,A
AU  - Wake,M
AU  - Acebrón-García-de-Eulate,M
AU  - Barritt,JD
AU  - Bubeck,D
AU  - Rouse,SL
DO  - 10.1016/j.celrep.2026.117044
PY  - 2026///
SN  - 2211-1247
TI  - Structural basis for Rep-mediated adeno-associated virus packaging
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2026.117044
UR  - https://doi.org/10.1016/j.celrep.2026.117044
VL  - 45
ER  - 

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