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1153-Confounding Noise in Multiplexed Enhancer AAV Screening

This research investigates the effectiveness of multiplexed enhancer screening for targeting specific cell types in the brain using adeno-associated viruses (AAVs). While traditionally validated one-by-one, the authors tested barcoded pools to accelerate discovery but encountered significant technical and biological noise that obscured true expression patterns. Key obstacles identified include AAV chimerism during pooled packaging, where DNA fragments recombine incorrectly, and transcriptional crosstalk between neighboring viral vectors. The study evaluates mitigation strategies like…

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