Synthetic cells produce therapeutic proteins inside tumors

The existing dogma is that protein medicines are produced in large-scale, and then injected to the patient. We propose to produce a protein of interest directly in the disease site, by utilizing nanotechnologies to achieve therapeutic precision and high functionality. The research approach is based on the development of synthetic therapeutic cells – miniature artificial inert “factories” that can be located in the body and latter remotely activated to synthesize a protein-based medicine only where it is needed. The produced protein can be tuned to the patient`s needs based on a predetermined DNA code which is incorporated inside these synthetic cells. We believe that this therapeutic platform can significantly increase treatment efficiency and reduce adverse effects to healthy tissues.

We developed a new cell free protein synthesis (CFPS) system (1) that was used to prepare liposomes (lipid particles) that act as artificial cells, capable of producing proteins autonomously in response to a physical trigger. Functional enzymes (luciferase and tyrosinase) and fluorescent proteins (Green fluorescent protein, GFP) were successfully produced using this system inside synthetic cells both in vitro and in vivo. In addition, the therapeutic capabilities of the synthetic cells were demonstrated by producing Pseudomonas exotoxin A (PE), an extremely potent protein, for treating cancer. Applying the particles on triple-negative breast cancer cells (4T1) in vitro or injecting them into a 4T1-induced tumor in vivo, resulted in high cytotoxicity due to the effective production of the therapeutic protein inside the vesicles (2).

Synthetic cells can serve as autonomous, trigger-able, artificial particles that produces a variety of proteins. I believe this platform can be applicative as a protein delivery system addressing the patients’ need, as well as to address a wide range of fundamental questions associated with protein synthesis in nature.

1. Krinsky, N., Kaduri, M., Shainsky-Roitman, J., Goldfeder, M., Ivanir, E., Benhar, I., & Schroeder, A. (2016). A Simple and Rapid Method for Preparing a Cell-Free Bacterial Lysate for Protein Synthesis.PloS one, 11(10).
2. Krinsky, N., Kaduri, M., Zinger, A., Shainsky‐Roitman, J., Goldfeder, M., Benhar, I., ... & Schroeder, A. (2018). Synthetic cells synthesize therapeutic proteins inside tumors. Advanced healthcare materials, 7(9), 1701163