Astrocyte engineering.

Tiling across the central nervous system, astrocytes contact synapses, blood vessels and other glial cells through highly specialised processes, allowing them to regulate local brain environments across multiple spatial and temporal scales. These anatomical and signalling features make astrocytes attractive substrates for modulating brain function and repair. Here, we frame "astrocyte engineering" as the intentional design of molecular access, sensing and effector modules in astrocytes to interrogate or modify local brain states. This Review focuses on how astrocyte interface biology can be converted into engineering logic, from genetic access and signalling perturbation to emerging sensor-effector designs. We first outline how astrocyte morphology, diversity and intercellular interactions shape the logic of cell-specific targeting. We then summarise tools for astrocyte-specific gene delivery and signalling control, including adeno-associated virus (AAV)-based strategies and G-protein coupled receptor (GPCR) signalling modulation approaches that can alter disease-relevant phenotypes. Further, we discuss recent proof-of-concept studies that equip astrocytes with new recognition or effector functions, including chimeric antigen receptor (CAR) astrocytes, synNotch-based systems, and trophic-factor delivery. We propose that future astrocyte engineering should be guided by omics-based design principles that link cell state, molecular access, input recognition, and effector selection.