An in vivo massively parallel platform for deciphering tissue-specific regulatory function [DNA]

Massively parallel reporter assays (MPRAs) have the potential to link differences in genome sequence, including genetic variants, to tissue-specific regulatory function. Whole-animal MPRA (WhAMPRA), where systemic intravenous AAV effectively transduces the plasmid MPRA library to mouse tissues. This technology simultaneously determines the transcriptional functions of hundreds of enhancers in vivo across multiple tissues A plasmid libratry with 642 synthetic enhancers and variants each with 20 DNA barcodes was transduced into C57BL6/J mice or transfected into HMC3 cells. DNA barcodes from viral DNA were then sequenced.