Synthetic Minimal Cells: A Novel Paradigm in Drug Delivery

The targeted delivery of therapeutics using liposomes is an important method to increase the therapeutic window and limit off-target effects of drugs. In recent years, the development of liposomes that can sense their environment and respond by releasing their payload have been developed to enhance site-specific delivery. However, engineering liposomes to sense and respond to diverse stimuli is challenging. At Synlife, we are developing synthetic minimal cells (SMCs) as a novel drug delivery platform to address these challenges.

Synthetic minimal cells comprise a biochemical mixture capable of gene expression (transcription and translation) and a nucleic acid template co-encapsulated in a liposome. By programming the nucleic acid template with genetic circuitry, it is possible to endow SMCs with complex sense and response behavior. This in turn enables the customization of SMC behavior, such as the sensing of localized disease biomarkers and responding by producing therapeutic proteins, pore proteins to release co-encapsulated small molecule drugs, or the release of diagnostic markers. The precision of this sense-and-respond behavior limits off-target effects, thereby increasing the therapeutic index of drugs that are too toxic to administer systemically.

Here, Synlife presents proof-of-concept experiments that demonstrate the programmability of SMCs and their ability to sense clinically relevant biomarkers and respond by producing drugs in situ.