Biomarker and Bioanalytical Readouts for the Development of AAV Gene Therapy

Recombinant adeno-associated virus (rAAV)-based gene therapy has been shown to be well-tolerated and effective for treating patients with genetic diseases. The technology approaches for clinical applications include gene replacement, gene addition, gene editing, and gene regulation. Gene therapy drug development requires complex and extensive collection of pharmacokinetic (PK) and biomarker readouts to support safety and efficacy evaluation as well as patient selection. This chapter provides a high-level overview of the following topics: viral biodistribution and shedding, pharmacodynamic (PD) biomarkers of transgene expression and changes of substrate and downstream pathway markers, assessment of genotoxicity risk caused by potential rAAV integration and off-target gene editing, biomarkers for immune-mediated toxicity, safety biomarkers for nonimmune organ-specific toxicity, and predictive and diagnostic biomarkers for study enrollment and patient stratification.