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. 2013 Jul 1;123(8):3317–3330. doi: 10.1172/JCI67930

Figure 7. Assessment of genotoxicity of the CCL-βAS3-FB LV vector.

Figure 7

(A) Frequency of vector IS in and near cancer-associated genes. The bars represent the frequencies of integrations in transcribed regions or within 50 kb of promoters of cancer-associated genes (in vitro, 32.1%; in vivo, 34.3%), as defined in Higgins et al. (44). (B) Integration frequency around TSS. The frequencies of vector IS in the four 5-kb bins in a 20-kb window centered at gene TSS are plotted. The IS are shown for the following: BM CD34+ cells analyzed after 2 weeks growth in vitro (lenti in vitro, n = 2091; gray bars) and 2–3 months in vivo engraftment in NSG mice (lenti in vivo, n = 414; black bars) along with an MLV γ-retroviral vector data set from a clinical gene therapy trial (MLV in vitro, n = 828; white bars) (45) and a random data set generated in silico and analyzed by identical methods (random, n = 12,837; black line). (C) IVIM assay. The replating frequencies for murine lineage-negative cells transduced with the different vectors are shown, calculated based on Poisson statistics using L-Calc software corrected for the bulk VC/cell measured by qPCR on day 8 pTD. The fractions presented across the lower portion of the figure represent the number of negative assays in which no clones were formed divided by the total number of assays performed for that vector. The horizontal bar represents the mean replating frequency of all positive assays. *P = 0.002, by 2-sided Fisher’s exact test.