General pharmacology PBPKQSP

Whole-body AAV8 gene-delivery and transgene-antibody PBPK

Reference paper ↗

Mechanistic mouse PBPK/QSP coupling whole-body AAV8 disposition, receptor-mediated cell entry, nuclear vector, nonlinear dose-dependent transgene expression, FcRn-aware trastuzumab PBPK, and delayed immune loss.

Therapeutic
AAV8-encoded trastuzumab
Modality
Gene-delivered antibody
Target
HER2 (antibody identity only, no target-binding module)
Disease
Preclinical AAV-mediated antibody delivery (not disease-specific)
Model type
PBPK, QSP

Complete model workspace

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Parameters
292
States
545
Equations
545
Derived outputs
6

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AAV8 2e10 vg/mouse IV

Rajwade 2026 fitted whole-body AAV8 and trastuzumab regimen at 2e10 vg per mouse.

Starting result

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Starting configuration

Time: 0–504 hour; step 6

InputDefaultAvailable range
AAV administered dose vg2.00e+10 11.00e+10–3.00e+10 1
AAV immune deg0.7 1/h0.35–1.05 1/h
AAV knuc0.027 1/h0.0135–0.0405 1/h
Kprod max1.28e-20 mol/h6.40e-21–1.92e-20 mol/h
Mab immune maximum elimination rate1.058 1/h0.529–1.587 1/h

Expected readouts

AAV8 in whole blood (vg/µL) · Perfused liver AAV8 (vg/ng DNA) · Plasma trastuzumab (µg/mL)

Adjustable model parameters

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How the model represents the biology

Mouse systems model linking an IV AAV8 dose to tissue vector genomes, intracellular transduction, secreted trastuzumab, whole-body antibody distribution, FcRn salvage, and vector/antibody immunogenicity losses.

AAV8-encoded trastuzumab initiates the modeled biology: Whole-body AAV8 biodistribution across 15 tissues, Receptor-mediated uptake and nuclear vector persistence, Dose-dependent transgene expression and secretion, FcRn-aware trastuzumab distribution and salvage, Vector and antibody immune-mediated clearance. Primary readouts are AAV8 in whole blood, Perfused liver AAV8, Plasma trastuzumab, Brain-interstitial trastuzumab, Delayed antibody immune loss.
Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID rajwade_2026_aav8_trastuzumab_nonlinear_pbpk.

Research use only — not for patient-specific prediction or dosing advice.

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