Fig. 6: DIRECTED enables specific targeting in complex environments.
From: Cell type-specific delivery by modular envelope design
a Cell type composition [in percent] of PBMCs as determined by flow cytometry after staining for specific surface markers. b Delivery efficiency of H2B-mCherry transgene to primary human T cells in PBMCs from three donors by VSV-G and VSV-Gdm+SNAP lentiviral vectors in the absence of antibody (VSV-Gdm) or functionalized with B cell targeting ligands (αCD19-BG, MegaCD40L-BG; VSV-Gdm-Bcell), T cell targeting ligands (αCD3-BG, αCD28-BG, αCD4-BG; VSV-Gdm-Tcell), or αCD3-BG (VSV-Gdm-αCD3). Shown is the percent of mCherry+ CD4+ (left, p-values: 0.083, 0.018666667, 0.004, 0.04, 0.032, 0.032) or mCherry+ CD8+ T cells (right, p-values: 0.050285714, 0.050285714, 0.004, 0.050285714, 0.333, 0.032). VSV-G and VSV-Gdm: MOI of 500, other variants: MOI of 250 (N = 2 infections per donor for 3 donors) c Delivery efficiency of H2B-mCherry transgene to primary human B cells in PBMCs from three donors by WT VSV-G, WT VSV-G+SNAP, VSV-Gdm+SNAP (VSV-Gdm), VSV-G+ αCD19-BG, MegaCD40L-BG (VSV-G-Bcell), and VSV-Gdm+ αCD19-BG, MegaCD40L-BG (VSV-Gdm-Bcell). VSV-G, VSV-G+SNAP and VSV-Gdm: MOI of 3500; VSV-Gdm-Bcell, and VSV-G-Bcell: MOI of 1750. (N = 2 independent infections per donor for 3 donors, p-values: 0.021, 0.883, 0.001, 0.627) d (left) Schematic highlighting defense mechanisms in whole blood. (right) Cell type composition of whole blood after removal of red blood cells. e Delivery efficiency of H2B-mCherry transgene to primary human T cells in whole blood from two donors by VSV-G and VSV-Gdm+SNAP lentiviral vectors in the absence of antibody (VSV-Gdm) or functionalized with T cell targeting ligands (VSV-Gdm-Tcell), or αCD3-BG (VSV-Gdm-αCD3). Shown is the percent of mCherry+ CD4+ T cells (left, p-values: 0.079, 0.037, 0.075) or mCherry+ CD8+ T cells (right, p-values: 0.014, 0.048, 0.161). VSV-G and VSV-Gdm: MOI of 1000; VSV-Gdm-Bcell, VSV-Gdm-Tcell, and VSV-Gdm-αCD3: MOI of 500. MOIs were calculated estimating 5000 leukocytes per μl of whole blood. (N = 2 infections per donor for 2 donors) Data are presented as mean ± standard deviation. Source data are provided as a Source Data file. For panel (b), a paired, two-sided Welch’s t-test with BH correction was used, and for panels (c) and (e), a two-sided Welch’s t-test was used. [ns, not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001].
