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Cell type-specific interfaces within living animals will be invaluable for achieving communication with identifiable cells over the long term, enabling applications across many scientific and medical fields. However, biological tissues exhibit complex and dynamic organization properties that pose serious challenges for chronic cell-specific interfacing. A new technology, combining chemistry and molecular biology, has emerged to address this challenge: genetically targeted chemical assembly (GTCA), in which specific cells are genetically programmed (even in wild-type or non-transgenic animals, including mammals) to chemically construct non-biological structures. Here, we discuss recent progress in genetically targeted construction of materials and outline opportunities that may expand the GTCA toolbox, including specific chemical processes involving novel monomers, catalysts and reaction regimes both de cellula (from the cell) and ad cellula (towards the cell); different GTCA-compatible reaction conditions with a focus on light-based patterning; and potential applications of GTCA in research and clinical settings. 

The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type–specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.