I-Corps: Secreted nucleic acid based gene reporter

这个i-Corps项目的更广泛的影响/商业潜力是极大地提高癌症和心血管退化等疾病的细胞疗法的有效性，这些疾病在2015年占美国死亡人数的近一半。细胞疗法包括将细胞移植到患者体内，目的是治疗疾病，例如靶向并杀死癌症的免疫细胞，或用于治疗糖尿病的胰岛素分泌细胞。一个主要的挑战是在细胞被引入后对其进行监测，无论是为了继续存活还是为了功能。这个i-Corp项目将探索一种技术的商业化潜力，这种技术可以用于目前的细胞疗法和开发新的细胞疗法。这项技术可以通过在实验室测试中提供治疗细胞在动物中如何发挥作用的关键信息，极大地降低数十亿美元的治疗开发成本，并可以显著提高生物制造效率，这一类别占生产细胞治疗成本的25%以上。i-Corps项目旨在开发一个技术平台，允许细胞通过将小RNA分子(条形码)分泌到血液中来报告其功能。根据它是如何被引入到细胞基因组中的，这种条形码可以报告细胞的持续持久性，或者报告细胞是否表达特定的基因，从而执行特定的功能。多个条形码可以组合在一起，同时报告蜂窝持久性和几种功能。这项技术将首次实现对动物体内植入细胞功能的监测。在未来，可能会设计抗癌的免疫细胞来表达条形码，并将这些细胞植入携带癌症的小鼠体内。该条形码将报告治疗细胞数量的增加或减少。还有可能通过分泌不同的条形码来设计细胞，使其在每次遇到癌细胞时进行报告。

The broader impact/commercial potential of this I-Corps project is to greatly enhance the effectiveness of cell therapies for diseases such as cancer and cardiovascular degeneration that accounted for almost half of all US deaths in 2015. Cellular therapies involve implanting cells into a patient with the goal of treating disease, such as immune cells to target and kill cancer or insulin-secreting cells for the treatment of diabetes. A major challenge is to monitor the cells after their introduction, both for continued survival and for function. This I-Corp project would explore the commercialize potential of a technology that could be used in current cell therapies and during development of new ones. This technology could dramatically reduce the multibillion-dollar therapeutic development costs by providing crucial information regarding how therapeutic cells function in animals during laboratory tests, and could significantly improve bio-manufacturing efficiency, a category that accounts for more than 25% of the cost to produce cell therapies.This I-Corps project aims to develop a technology platform that would allow cells to report on their function by secreting a small RNA molecule (barcode) into the bloodstream. Depending on how it is introduced into the genome of the cell, this barcode could report on the continued persistence of the cells or on whether the cells are expressing a particular gene and therefore performing a specific function. Multiple barcodes could be combined to report on cellular persistence and several functions simultaneously. This technology will allow, for the first time, the monitoring of function of implanted cells inside animals. In the future, it may be possible to engineer cancer-fighting immune cells to express a barcode and implant the cells into mice bearing cancer. This barcode will report on the increase or decrease of the number of therapeutic cells. It may also be possible to engineer the cells to report each time a cancer cell is encountered by secreting a different barcode.