Fig. 5: In vivo base editing in NHPs with optimized AAV-SABE1.
From: High-efficiency base editing in the retina in primates and human tissues
a, Alkaline gel electrophoresis image (left) and 2D-ddPCR (right) of SABE1(N) and SABE1(C) packaged into AAV5-v1 (1–2), AAV5-v2 (3–4) or AAV9-PHP.eB (5–6). GOI, gene of interest. b, Schematic showing the key differences between the AAV5-v1 (top) and AAV5-v2 (bottom) Rep/Cap packaging plasmids. c, Experimental design showing different injection conditions, the number of eyes injected and the number of eyes in which the fovea was detached (in brackets). Illustration in c created with BioRender.com. d, In vivo base-editing efficiencies in the retina in gDNA and ABCA4 mRNA with AAV5-v2-SABE1 (left) and AAV9-PHP.eB-SABE1 (right) at different dose levels. Results are presented as the mean ± s.d. The dashed lines indicate editing rates using AAV5-v1 at 1 × 1011 v.g. per eye (left) or AAV5-v1 at 3 × 1011 v.g. per eye (right); data are from Fig. 4e. Fold improvements compared to AAV5-v1 are indicated above the bars. e, In vivo base-editing efficiencies in the RPE/choroid in gDNA and ABCA4 mRNA with AAV5-v2-SABE1 (left) and AAV9-PHP.eB-SABE1 (right) at different dose levels. Results are presented as the mean ± s.d. The dashed lines indicate editing rates using AAV5-v1 at 1 × 1011 v.g. per eye (left) or AAV5-v1 at 3 × 1011 v.g. per eye (right); data are from Fig. 4f. Fold improvements compared to AAV5-v1 are indicated above the bars. f, In vivo base-editing efficiencies in gDNA of sorted cones and rods with AAV5-v2-SABE1 (left) and AAV9-PHP.eB-SABE1 (right) at different dose levels. Results are presented as the mean ± s.d. The dashed lines indicate editing rates using AAV5-v1 at 1 × 1011 v.g. per eye (left) or AAV5-v1 at 3 × 1011 v.g. per eye (right); data are from Fig. 4g. Fold improvements compared to AAV5-v1 are indicated above the bars. g, In vivo base-editing efficiencies in the foveal retina and RPE/choroid with AAV5-v2-SABE1 (left) and AAV9-PHP.eB-SABE1 (right) at different dose levels. Results are presented as the mean.
