Agent-Based ModelDerived from module7 elements · 6 transitions
Agent-based hepatocyte ASGR1/ASGR2 GalNAc-conjugate uptake, receptor recycling, lysosomal routing, and cytosolic escape model
Simulates 100 discrete receptor-ligand / GalNAc-conjugate agents traversing the seven stages of hepatocyte ASGR-mediated uptake under uniform uncalibrated default transition rates (base_rate = 0.45, competing_inhibitor_factor = 0.25). Under wild-type baseline conditions, active RAB7A/ESCRT late endosomal maturation (escrt_rab7_late_endosome) attenuates the cytosolic escape transition from acidified sorting endosomes, yielding ~47% receptor recycling (ehd1_receptor_recycling), ~43% lysosomal routing/degradation (ctsd_lysosomal_degradation), and ~10% productive cytosolic escape (cytosolic_galnac_escape). Note that these percentages arise from uniform uncalibrated ABM transition kinetics rather than calibrated clinical pharmacokinetics (where only a minuscule portion of endocytosed GalNAc-ASO/siRNA escapes into the cytosol in vivo; PMID:29069408), and the RAB7A-depletion escape enhancement (10% -> 47%) is a qualitative cross-modality extrapolation from hepatic LNP endosomal escape competition (PMID:41814093). Perturbing individual stages reproduces the qualitative directionality of ASGR/clathrin uptake blockade, V-ATPase inhibition, EHD1 recycling loss, and RAB7A depletion.