Synthetic Cells Synthesize Therapeutic Proteins inside Tumors
| Autor: | Assaf Zinger, Dov Hershkovitz, Itai Benhar, Avi Schroeder, Nitzan Krinsky, Maya Kaduri, Mor Goldfeder, Janna Shainsky-Roitman |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Virulence Factors Cell Bacterial Toxins Green Fluorescent Proteins Biomedical Engineering Pharmaceutical Science Exotoxins Article Green fluorescent protein Biomaterials 03 medical and health sciences chemistry.chemical_compound Mice Cell Line Tumor medicine Protein biosynthesis Tumor Microenvironment Pseudomonas exotoxin Animals Secretion chemistry.chemical_classification ADP Ribose Transferases Mice Inbred BALB C Chemistry RNA Neoplasms Experimental Amino acid Cell biology 030104 developmental biology medicine.anatomical_structure Nanoparticles Artificial Cells Female DNA |
| Zdroj: | Advanced Healthcare Materials |
| ISSN: | 2192-2659 |
| Popis: | Protocells, 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, we show for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anti-cancer proteins inside tumors. The particles were 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 protocells synthesized, up to 2×10(7) copies of superfolder green fluorescent protein (sfGFP) were synthesized in each liposome. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, were synthesized inside the particles. Incubating protein producing particles, 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, indicating robust apoptosis. Protein producing particles are synthetic-biology platforms capable of synthesizing therapeutic proteins on-demand. |
| Databáze: | OpenAIRE |
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