Geneticability of Live‐Cell Site‐Specific Synthesis of Quantum Dots

Abstract Molecular‐scale integration of non‐natural functional components into living systems for precise manipulation, monitoring, and enhancement of organisms remains a great challenge. Here, we achieved the geneticable synthesis of functional inorganic nanomaterials with molecular‐level spatial precision within live mammalian cells. By genetically encoding a cysteine‐rich protein tag named 1DFS, and tuning its intracellular inherent metabolic pathways, organic molecules can be precisely synergized with inorganic molecules at a specific site of the protein of interest within live cells to grow a single inorganic semiconductor nanocrystal‐specifically quantum dot (QD). This, in turn, endows the protein with unique fluorescent functions for precise and stable protein labeling even after multiple cell passages. This approach is flexible and universal, and QD can not only integrate into the specific protein in live cells but also synchronously grow on the delicate viral nucleoprotein (NP) during the natural replication and assembly of virions in the host cells. The labeled NPs then accurately assemble into viral ribonucleoproteins deep inside virions, resulting in fluorescent virions with full infectivity that exceeds capabilities of conventional genetic manipulation. This work provides a programmable platform for geneticable growth of inorganic nanomaterials at specific molecular sites, opening a new frontier in precise inorganic‐enabled synthetic biology.