Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk
Fig 2
Mucosal gene therapy depends on a strong proliferative advantage of gene-corrected cells.
(A) 10 gene-corrected cells (green) were tracked over 50 years in a 0.67 mm2 FA mucosal tissue section (100 replicate simulations per condition). The gene correction fates were tracked to identify simulations reaching confluence (80% of basal layer cells corrected, red box) or loss (no remaining gene-corrected cells, blue box). (B) Number of simulations achieving confluence (red), loss (blue), or ongoing expansion (orange) at 50 years as a function of persistence coefficient ( = 0, 0.001, 0.01, 0.2, 0.5, 1). (C) Time at which simulations reached confluence or loss as a function of persistence coefficient, with mean times for each
indicated in black (+) and outcome of individual simulations as points. Gene-corrected patches not reaching confluence or loss by 50 years are not plotted. (D) Number and size of gene-corrected patches at 1 year as a function of persistence coefficient
. (E) Average area of confluent gene-corrected patches as a function of time and persistence coefficient
. Bars indicate interquartile ranges.