Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk
Fig 3
Higher corrected cell numbers and optimal spacing can increase the likelihood of tissue replacement despite clonal interference.
Gene-corrected patch loss probability and time to confluence as a function of corrected cell number (A-C) and spatial delivery distribution (D-F). 100 simulations/condition were run for each persistence coefficient , with error bars indicating binomial errors (B,E) or interquartile ranges (C, F). (A) Initial spatial distribution of gene-corrected cells (
cells, in green) with a constant diffusion coefficient (
). Probability of gene-corrected patch loss (B) and time to confluence (C) as a function of persistence coefficient (
) and initial corrected cell number (
). (D) Initial spatial distribution of ten gene-corrected cells (green) as a function of diffusion coefficient (
, corresponding to low, medium and high diffusion). Probability of gene-corrected patch loss (E) and time to confluence (F) as a function of persistence coefficient (
) and diffusion coefficient (
). Visualizations of gene-corrected cell patches ten years after correction as a function of microneedle spacing (G) or density (H) on 10.67 mm² tissue sections. Initial arrayed delivery shown in panel insets, and each color represents the descendants of a single microneedle that corrects
cells with
. Areas of corrected cell patches at ten years are quantified in the lower right corner of each tissue section.