Bacterial Minicells for Cancer Therapeutics

描述（由申请人提供）：活细胞中具有预测功能的遗传电路的工程设计代表了合成生物学扩展领域的定义焦点。自从最初的拨动开关和振荡器设计以来，已经构建了控制细胞群体生长、检测图像中的边缘以及计数离散细胞事件的遗传电路。遗传电路的一个有希望的应用是对生物体进行编程，使其充当智能传感和传递装置，以摧毁人体内的恶性细胞。尽管细菌疗法已被用于治疗癌症，但它们的成功有限，因为它们固有的过度生长和毒性、无法穿透肿瘤环境以及特异性是需要克服的挑战性问题。在这里，我们建议使用细菌“微细胞”作为运载工具，利用合成基因电路选择性地将货物运送到癌细胞。微细胞是由细菌中异常细胞分裂产生的球形纳米颗粒，不含染色体。它们能够维持质粒，产生能量，消耗氧气，转录和翻译DNA，但重要的是它们不能生长和分裂。因此，微细胞可以被工程化以通过感测环境和在体内递送治疗剂来采用智能决策，同时避免与活细菌载体相关的功效问题。

DESCRIPTION (provided by applicant): The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic bioloy. Since the original toggle switch and oscillator designs, genetic circuits have been constructed that control cellular population growth, detect edges in an image, and count discrete cellular events. One promising application of genetic circuits is to program an organism to act as an intelligent sensing and delivery device to destroy malignant cells inside the human body. Although bacterial therapies have been used to treat cancer, they have met with limited success because their inherent overgrowth and toxicity, inability to penetrate tumor environments, and specificity are challenging issues to overcome. Here, we propose to use bacterial "minicells" as delivery vehicles that utilize synthetic gene circuitry to selectively deliver cargo to cancer cell. Minicells are spherical nanoparticles that are produced from aberrant cell divisions in bacteria and contain no chromosome. They are able to maintain plasmids, produce energy, consume oxygen, transcribe and translate DNA, but importantly they are not able to grow and divide. Therefore, minicells can be engineered to employ intelligent decision-making by sensing the environment and delivering therapeutics in-vivo while the avoiding the efficacy issues associated with live bacterial vectors.