TY - JOUR
T1 - Synthetic Cells Synthesize Therapeutic Proteins inside Tumors
AU - Krinsky, Nitzan
AU - Kaduri, Maya
AU - Zinger, Assaf
AU - Shainsky-Roitman, Janna
AU - Goldfeder, Mor
AU - Benhar, Itai
AU - Hershkovitz, Dov
AU - Schroeder, Avi
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/5/9
Y1 - 2018/5/9
N2 - 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.
AB - 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.
KW - biologics
KW - breast cancer
KW - nanoparticles
KW - nanotechnology
KW - origin of life
KW - personalized medicine
KW - protein drugs
KW - protocells
KW - synthetic cells
UR - http://www.scopus.com/inward/record.url?scp=85039174319&partnerID=8YFLogxK
U2 - 10.1002/adhm.201701163
DO - 10.1002/adhm.201701163
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AN - SCOPUS:85039174319
SN - 2192-2640
VL - 7
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 9
M1 - 1701163
ER -