CTCF regulates wild-type and recombinant AAV gene expression by shaping viral chromatin.

CTCF binding to the wtAAV2 genome—via a CBE upstream of the P5 promoter—is linked to up to four-fold higher rAAV transduction efficiency and GFP expression across multiple cell types.

• Why it matters: rAAV vectors lack regulatory elements outside the ITR, limiting control of viral gene expression and reducing therapeutic transgene output.
• What they did: Using in silico analysis, biochemical pulldowns, and high-throughput sequencing, the study mapped CTCF association to wtAAV2 but not rAAV; global knockdown and CBE deletion then tested function, followed by re-engineered rAAV2 vectors carrying the wtAAV2-CBE and CUT&RUN.
• The result: CTCF-mediated chromatin remodeling made the CBE necessary and sufficient to regulate wtAAV2/rAAV2 chromatin and increased nascent vector RNA transcripts, improving rAAV performance independently of capsid serotype.

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