Bioengineering lipid-based synthetic cells for therapeutic protein delivery.

Synthetic cells (SCs) offer a promising approach for therapeutic protein delivery, combining principles from synthetic biology and drug delivery. Engineered to mimic natural cells, SCs provide biocompatibility and versatility, with precise control over their architecture and composition. Protein production is essential in living cells, and SCs aim to replicate this process using compartmentalized cell-free protein synthesis systems within lipid bilayers. Lipid bilayers serve as favored membranes in SC design due to their similarity to the biological cell membrane. Moreover, engineering lipidic membranes enable tissue-specific targeting and immune evasion, while stimulus-responsive SCs allow for triggered protein production and release. This Review explores lipid-based SCs as platforms for therapeutic protein delivery, discussing their design principles, functional attributes, and translational challenges and potential.