Synthetic Cells Synthesize Therapeutic Proteins inside Tumors

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

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

Keywords

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

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