Fig. 3: CAP-Mac is biased towards neurons throughout infant green monkey and newborn rhesus macaque brains.
a, Distribution of IV CAP-Mac expression in 2-day-old rhesus macaques (5 × 1013 vg kg−1 via the saphenous vein) across coronal slices showing fluorescent reporter expression (ssCAG-mNeonGreen, ssCAG-mRuby2 and ssCAG-mTurquoise2) in the cortical and subcortical brain regions (insets). Imaging channels of reporters are identically pseudo-coloured. b, Co-localization of fluorescent reporters with NeuN (neurons) or S100β (astrocytes) in 2-day-old rhesus macaques treated with CAP-Mac (n = 2 macaques). Values are reported as a percentage of all the XFP+ cells. Mean [XFP+NeuN+]/XFP+ range between 47% and 60% and mean [XFP + S100β+]/XFP+ between 0% and 3%. Overall, CAP-Mac targeted 1.12% and 0.04% of all NeuN+ and S100β+ cells, respectively. c, Representative images from 8-month-old green monkeys intravenously dosed with CAP-Mac (top) or AAV9 (bottom) packaging ssCAG-eGFP (7.5 × 1013 vg kg−1 via the saphenous vein). d,e, Co-localization of fluorescent reporters with NeuN (neurons) or S100β (astrocytes) in infant green monkeys treated with CAP-Mac (d; n = 2 green monkeys) or AAV9 (e; n = 2 green monkeys). Values are reported as a percentage of all the GFP+ cells. CAP-Mac, mean [GFP+NeuN+]/GFP+ between 33% and 51% and mean [GFP+S100β+]/GFP+ between 3% and 21%. AAV9, mean [GFP+NeuN+]/GFP+ between 2% and 10% and mean [GFP+S100β+]/GFP+ between 23% and 59%. Overall, CAP-Mac targeted 1.30% and 0.64% of NeuN+ and S100β+ cells, respectively, in the green monkey brain. In contrast, AAV9 targeted 0.49% of NeuN+ cells and 1.86% of S100β+ cells. f, Distribution of CAP-Mac- and AAV9-delivered eGFP transgene in 11 brain regions of green monkeys (n = 4 green monkeys). Each data point represents the measured vector genomes per microgram of total DNA in a section of tissue from each region and monkey. Mean values ± s.e.m. are shown.
