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Synthetic Cells Synthesize Therapeutic Proteins inside Tumors
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-12-28 , DOI: 10.1002/adhm.201701163
Nitzan Krinsky 1, 2 , Maya Kaduri 1 , Assaf Zinger 1 , Janna Shainsky-Roitman 1 , Mor Goldfeder 1 , Itai Benhar 3 , Dov Hershkovitz 4 , Avi Schroeder 1
Affiliation  

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.

中文翻译:


合成细胞在肿瘤内合成治疗性蛋白质



合成细胞,即人造细胞样颗粒,能够基于 DNA 模板自主合成 RNA 和蛋白质,是研究细胞功能和揭示生命起源的新兴平台。在这里,首次证明基于人工脂质的囊泡含有转录和翻译所需的分子机制,可用于在肿瘤内合成抗癌蛋白。合成细胞被设计为独立系统,从其生物微环境中获取营养物质以触发蛋白质合成。当预先加载模板 DNA、氨基酸和供能分子时,每个合成细胞中会合成多达 2 × 10 7个绿色荧光蛋白拷贝。颗粒内部合成了多种分子量达到 66 kDa 且具有诊断和治疗活性的蛋白质。将编码为分泌假单胞菌外毒素 A (PE) 的合成细胞与培养的 4T1 乳腺癌细胞一起孵育,可杀死大多数恶性细胞。在携带 4T1 肿瘤的小鼠中,局部注射产生 PE 的颗粒后对肿瘤组织的组织学评估表明细胞凋亡强劲。合成细胞是在患病组织中按需合成治疗性蛋白质的新平台。
更新日期:2017-12-28
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