Liu 2026 full AAV-mediated anti-TargetX rat brain QSP reconstruction
Mechanistic rat QSP coupling whole-body AAV biodistribution, intracellular transduction, transgene-derived anti-TargetX mAb, FcRn-aware protein PBPK, TargetX binding, and detailed brain/CSF transport across 725 explicit scalar states.
- Therapeutic
- AAV9/AAV5-encoded anti-TargetX monoclonal antibody
- Target
- TargetX (anonymized paper target)
- Disease
- Not reported
Biological model
Mechanistic rat QSP linking IV, intracisterna-magna, or intrastriatal AAV delivery to whole-body vector disposition, transgene-derived anti-TargetX antibody, FcRn-aware protein distribution, and free TargetX in plasma, brain ISF, and CSF.
Model details
Mechanistic rat QSP coupling whole-body AAV biodistribution, intracellular transduction, transgene-derived anti-TargetX mAb, FcRn-aware protein PBPK, TargetX binding, and detailed brain/CSF transport across 725 explicit scalar states.
Modeled states
- adipose free intracellular endothelial AAV1/L
adipose free intracellular endothelial AAV
- adipose free endothelial abluminal receptor1/L
adipose free endothelial abluminal receptor
- adipose bound endothelial abluminal receptor1/L
adipose bound endothelial abluminal receptor
- adipose free endothelial luminal receptor1/L
adipose free endothelial luminal receptor
- adipose bound endothelial luminal receptor1/L
adipose bound endothelial luminal receptor
- adipose endothelial nuclear dsDNA AAV1/L
adipose endothelial nuclear dsDNA AAV
- adipose free intracellular endothelial receptor1/L
adipose free intracellular endothelial receptor
- adipose bound intracellular endothelial receptor1/L
adipose bound intracellular endothelial receptor
- AAV in adipose interstitium1/L
AAV in adipose interstitium
- adipose free intracellular parenchymal AAV1/L
adipose free intracellular parenchymal AAV
- adipose free parenchymal membrane receptor1/L
adipose free parenchymal membrane receptor
- adipose bound parenchymal membrane receptor1/L
adipose bound parenchymal membrane receptor
Key readouts
- AAV in whole bloodVg/mL
Whole-blood vector-genome concentration for route and serotype biodistribution comparison.
- AAV in total brainVg/mL
Volume-weighted vector-genome concentration across modeled brain vascular, barrier, CSF, meningeal, and cellular spaces.
- Anti-TargetX mAb in plasmanM
Circulating transgene-derived or exogenously dosed antibody.
- Anti-TargetX mAb in total brainnM
Volume-weighted modeled antibody across brain vascular, ISF, BBB, BCSFB, and parenchymal endosomal spaces.
- Free TargetX in cisterna-magna CSF% baseline
Free cisterna-magna TargetX normalized to its pre-dose model baseline; this is the Figure 7 CSF mapping.
Explore this model
Choose a starting point to view its result. Adjust key model inputs when you want to explore a different outcome.
Full-system structural integration
Short integration of all 725 states without dosing.
Questions to explore
- Does the complete 725-state system integrate without a dose?
Starting result
This result reflects the starting settings. Run your changes to update it.
Model inputs
Five scientist-facing controls at most.
Compare a parameter
How does one model input change the response?
Does the complete 725-state system integrate without a dose?
aav kd copy L
Compare this model input while holding the other settings fixed.
Exploratory range around the default value.
5 evenly spaced values in 1/L. Other model inputs and the simulation window stay fixed.
Interpret with care
- Research-only rat forward simulation; do not interpret as a dose recommendation, clinical prediction, or sponsor-fit replay.
- Figures 3–6 comparisons use raster-derived sponsor population-fit curves and therefore establish diagnostic public-figure consistency rather than parity to unreleased source coordinates.
Review the server-confirmed fixed price before starting the comparison.
Comparative response
End-of-window response across the selected parameter values.
Choose an exploratory range around the default, review the fixed price, and run the comparison.
Scientific reference
Supporting publication
QSP model for AAV-mediated antibody delivery in rat brainJournal of Pharmacokinetics and Pharmacodynamics
