Structural basis for Rep-mediated adeno-associated virus packaging - PubMed
5 days ago
- #gene therapy
- #cryo-EM
- #viral vectors
- Adeno-associated viruses (AAVs) are used as gene therapy vectors, but their packaging mechanism is not fully understood.
- Cryo-EM structures reveal the Rep helicase packaging motor's interaction with packaging marker DNA (ITR) and the AAV8 capsid.
- Rep-ITR complexes show dynamic oligomeric states on DNA, explaining the strand separation mechanism linked to its ATPase cycle.
- Rep binds preferentially to empty capsids, with a likely conserved binding interface across the virus family.
- A cryptic capsid ATP-binding site is identified, triggering structural changes that prepare the capsid for packaging.
- These findings enhance understanding of Rep-mediated packaging, impacting parvovirus virology and viral vector design.