A new design framework for adeno‑associated virus (AAV) vectors enables dynamic responses to tumor microenvironment cues, improving tumor targeting and intratumoral delivery in preclinical models. The approach addresses long‑standing barriers in viral vector specificity for solid tumors. Developers incorporated sensor elements and regulatory circuits into AAV capsids and expression cassettes to restrict activity to tumor niches. The platform could accelerate gene therapy approaches for oncology by reducing off‑target expression and improving therapeutic index across gene‑delivery programs.