Integrating CRISPR-Cas Technology into Organic Electronics for Rapid Point-of-Care Genotyping

这项提案旨在解决新生儿感染治疗中未得到满足的一个关键需求。庆大霉素是一种抗生素，可以有效地治疗各种感染，每年有10万名婴儿使用庆大霉素。这种治疗需要在重症监护病房中婴儿出现的第一个小时内进行，也就是“黄金时段”。然而，每500个婴儿中就有一个携带RNR1基因的变化，这使他们容易患上完全性和不可逆转的耳聋。这种变化的基因检测至少需要两天时间，所以无法及时得出结果，通过允许使用不同的抗生素来预防这些婴儿的听力损失。2020年，我们的团队开发了世界上第一个可以在婴儿床边进行的护理点基因测试。这项测试需要26分钟，可以安全地使用抗生素。在最近的一项研究中，我们表明，这项测试通过在三个婴儿中预防耳聋和不延误抗生素治疗来发挥作用。尽管这一系统取得了成功，但我们需要开发一种更快的不同系统，以确保有效治疗不会延误。因此，对新的技术解决方案的需求显然没有得到满足，以提供更快的护理点基因检测，这被称为研究问题。在这项研究中，我们建议开发一种新型的、快速的护理点设备，能够比目前的方法更快地检测RNR1基因的变化。该设备将结合一种新的基因识别技术和一个有机电子设备平台，能够快速(1分钟)电子读出感兴趣的基因变化。我们称之为研究解决方案。这项研究将开发这种电子设备，并将其与面颊拭子样本中的DNA进行测试，以表明它可以用于人类样本。总的来说，这项提议旨在开发一种新一代诊断工具，可以支持在主流临床实践中实施快速基因检测，改善患者和医疗系统的结果。事实上，我们在这里建议开发的设备可以用于测试对人类健康至关重要的其他基因变化，而这些变化需要迅速得到结果。

This proposal aims to address a critical unmet need in the treatment of infections in newborn babies. Gentamicin is an antibiotic that is effective in the treatment of a wide range of infections and is used in 100,000 babies per year. This treatment is required in the first hour, "the golden hour" of a baby being seen in the intensive care unit. However, 1 in 500 babies carry a change in their RNR1 gene that predisposes them to complete and irreversible deafness. Genetic testing for this change takes a minimum of two days and so a result is not available in time to prevent the hearing loss in these babies by allowing use of a different antibiotic.In 2020, our team developed the world's first point of care genetic test that can be carried out at the baby's bedside. This test takes 26 minutes and allows safe use of the antibiotic. In a recent study, we showed that the test worked by preventing deafness in three babies and by not delaying antibiotic treatment. Despite the success of this system, we need to develop a different system that is quicker to ensure that there are no delays to effective treatment. As such, there is a clear unmet need for new technological solutions to deliver even more rapid point-of-care genetic testing this is called the Research Problem.In this study, we propose to develop a novel, rapid point-of-care device that is capable of detecting changes in the RNR1 gene more quickly than the current approach. This device will combine a novel gene recognition technology with an organic electronic device platform that is capable of rapid (< 1 min) electronic readout of the gene change of interest. We call this the Research Solution. This research will develop the electronic device and test it with DNA from cheek swab samples, to show that it can be used with human samples.Overall, this proposal aims to develop a next generation diagnostic tool that could support the implementation of rapid genetic testing in mainstream clinical practice, improving outcomes for patients and the healthcare system. Indeed, the device that we propose to develop here could be used for the testing other gene changes important in human health, where a result is required rapidly.