Extended Data Fig. 5: Characterization of tissue-specific expression of dual-AAV PHP.eB TadCBEd with PRNP R37X F+E-sgRNA strategy.
From: In vivo base editing extends lifespan of a humanized mouse model of prion disease
a, Viral genome concentration normalized to the diploid genome (vg/dg) in the liver of Tg25109 mice untreated (n=6), or treated with dual-AAV PHP.eB TadCBEd PRNP R37X F+E-sgRNA with the Cbh promoter (Cbh; n=6), hSYN promoter (hSYN; n=6), hSYN promoter with miR-183 target sites incorporation (hSYN+miR-183; n=6), hSYN promoter with miR-122 target sites incorporation (hSYN+miR-122; n=5), or hSYN promoter with miR-183 and miR-122 target sites incorporation (hSYN+miR-183+miR-122; n=5) at a total dose of 1.5x1013 vg/kg. ddPCR was performed with probes specific for Cas9 N- and C-terminus, and Actb housekeeping gene. b and c, Cargo transgene transcript normalized to Gusb transcript in the liver (b) and DRG (c) of mice treated with dual-AAV PHP.eB TadCBEd PRNP R37X F+E-sgRNA, with Cbh promoter (Cbh; n=6), hSYN promoter (hSYN; n=6), or hSYN promoter with miR-183 and miR-122 target site incorporation (hSYN+miR183+miR122; n=4). ddPCR was performed with probes specific for Cas9 N- and C-terminus, and Gusb transcript. Dots represent individual biological replicates and data are presented as mean values +/− 95% CI.
