Synthetic Cells Synthesize Therapeutic Proteins inside Tumors

Nitzan Krinsky, Maya Kaduri, Assaf Zinger, Janna Shainsky-Roitman, Mor Goldfeder, Itai Benhar, Dov Hershkovitz, Avi Schroeder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Synthetic cells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the origins-of-life. Here, it is shown for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules, up to 2 × 107 copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on-demand in diseased tissues.

Original languageEnglish
Article number1701163
JournalAdvanced healthcare materials
Volume7
Issue number9
DOIs
StatePublished - 9 May 2018

Funding

FundersFunder number
Alon and Taub Fellowships
Baroness Ariane de Rothschild Women Doctoral Program
European Union FP-7908049
Israel Ministry of Economy52752
Israel Ministry of Science Technology and Space – Office of the Chief Scientist
Lorry I. Lokey Interdisciplinary Center for Life Sciences & Engineering
Mallat Family Foundation
Russell Berrie Nanotechnology Institute
Technion Integrated Cancer Center
Horizon 2020 Framework Programme680242
Chief Scientist Office, Scottish Government Health and Social Care Directorate3-11878
German-Israeli Foundation for Scientific Research and DevelopmentI-2328-1139.10/2012
Israel Cancer Association2015-0116
Israel Science Foundation1778/13
Ministry of Science and Technology, Israel

    Keywords

    • biologics
    • breast cancer
    • nanoparticles
    • nanotechnology
    • origin of life
    • personalized medicine
    • protein drugs
    • protocells
    • synthetic cells

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