Engineered AAVs can be used to specifically induce necroptosis of tumor cells in vitro. Engineered AAVs can be used to specifically induce necroptosis.

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Engineered AAVs can be used to specifically induce necroptosis of tumor cells in vitro. Engineered AAVs can be used to specifically induce necroptosis of tumor cells in vitro. (A) Schematic of AAVs used to transduce tumor cells to express engineered pro-death enzymes fused to a constitutively oligomerizing (co) recruitment domain under the control of a synthetic MND promoter, leading to subsequent induction of a corresponding PCD modality. (B and C) Validation and kinetics of AAV2.5 serotype transduction efficiency in B16.F10 cells in vitro. (B) Percent of GFP+ cells transduced with AAV2.5-eGFP control. (C) Percent cell death in cells transduced with various death-inducing constructs. n = 3 technical replicates per group. (D) Heatmap depicting relative expression values of NF-κB–dependent gene targets, chemokines, and cytokines via NanoString analysis of B16.F10 tumor cells compared to eGFP-transduced controls 10 hours after AAV2.5 transduction (1 × 1011 IFU). Data are representative plots from two independent experiments (B and C) or means of three technical replicates from one experiment (D). Annelise G. Snyder et al. Sci. Immunol. 2019;4:eaaw2004 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works