Optical Control of Therapeutic Synthetic Cells: Controlling Biomolecule Synthesis, Activation, and Communication.

Synthetic cells are emerging as promising platforms that combine cell-free biomolecule synthesis with the programmability of bottom-up engineered compartments. By decoupling biomolecule production from cellular growth and evolutionary constraints, synthetic cells enable the controlled generation of proteins, nucleic acids, peptides, and signaling molecules within defined artificial environments. However, many envisioned biomedical applications require precise regulation over biomolecule synthesis, activation, transport, release, and communication. In this Review, we examine how light can provide spatiotemporal control over synthetic cell functions relevant to future therapeutic applications. We compare external control modalities and review optical strategies that regulate synthetic cell functions across multiple functional layers, including biomolecule synthesis, activation, transport and release, communication, and systems-level integration. Particular emphasis is placed on integrating optical control with cell-free expression systems, RNA-based regulatory platforms, membrane engineering, and emerging synthetic cell architectures. We further discuss challenges associated with system integration, biomolecule complexity, energy management, light delivery, and translation. By classifying optical methodologies according to the functional layers they regulate, we provide a methodology-centered framework for comparing and integrating optical-control strategies toward increasingly sophisticated light-responsive synthetic cell platforms for future therapeutic applications.