Quantitative Systems Pharmacology Modeling of Adeno-Associated Virus Gene Therapies: Mechanistic Identification of Species-Translation Using Preclinical and Clinical Data

The authors discuss testing model predictions of liver transduction dose-dependency and kinetics in hemophilia gene therapies, cross-species translation of AAV8 gene therapy responses and the calibration to clinical data, and then discuss allometric scaling of kinetic rates of intracellular AAV processes and leveraging human data for assessing inter-patient variability and dose-response prediction. Finally, the authors describe innovative nonlinear compartmental models of AAV gene therapy dynamics in great detail.