Figure 5.

The “enter-and-express” phenotype is mainly driven by VR-I of AAV8 origin, AAV10's VR-IV, and AAV7's VR-VII

(A) Schematic representation of AAV swapped used in this part of the study. VR origins are shown for reference as colored blocks. (B–C) In vivo comparison of AAV-SYD12, AAV8, and swapped variants in high-RI hFRGs (n = 2). (B) Percentage of NGS reads mapped to each AAV capsid (sum of n = 4 barcodes/capsid) in human hepatocytes at the DNA (vector uptake, molecular transduction) and cDNA (expression, functional transduction) levels, normalized to the pre-injection mix, is shown. (C) EXIs (raw cDNA read percentage/raw DNA read percentage) of the swapped variants in the same high-RI hFRGs. (D) Representative immunofluorescence analysis of a humanized FRG liver transduced with AAV8-Cerulean and AAV-SYD12-Venus. Red: human GAPDH; cyan: AAV8 vector-expressed Cerulean; yellow: AAV-SYD12 vector-expressed Venus; blue: DAPI (nuclei). Scale = 100 μm. (E) FACS analysis of the percentage of Venus-positive and Cerulean-positive human and murine hepatocytes in the humanized FRG mouse shown in (D). (F and G) Equivalent analyses as in (D and E) for AAV8-EC-Venus and AAV8-Cerulean. (H and I) Equivalent analyses as in (D and E) for AAV7-EC-Venus and AAV7-Cerulean.