I-Corps: Targeted Epigenetic Modulation to Activate Therapeutic Genes

这个I-Corps项目的更广泛的影响/商业潜力是开发一个遗传医学平台，以调节人类基因来治疗特定疾病。许多疾病是由特定基因的异常水平引起的，这可能会产生有害影响。目前的技术可能会通过提供极高水平的基因来过度补偿，从而造成不必要的影响。这项技术旨在以可控和可逆的方式激活人类基因组中的特定基因。通过使用细胞自身的机制，所提出的技术可以精确地控制基因表达，以治疗分子被递送的疾病。如果成功，这项技术可能为各种疾病提供新的治疗方法，为患者带来更好的健康结果。此外，这项技术可能为药物开发提供新的平台。I-Corps项目的基础是开发一种新的遗传医学平台，该平台使用基于CRISPR/Cas的表观基因组编辑，通过上调治疗基因来治疗疾病。目前现有的方法在靶向基因组的特定非编码区方面效率不高。相比之下，所提出的技术旨在靶向人类细胞中与某些疾病状态有关的非编码基因组区域并恢复其功能。此外，所提出的技术能够有效地递送这些分子，降低细胞毒性和脱靶效应，同时保留功能。这可以克服在体内递送这些疗法以达到更高水平的治疗靶向功效方面的现有障碍。这项技术有可能治疗多种单基因和复杂的疾病，这些疾病以前无法通过目前的治疗方法获得。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a genetic medicine platform to regulate human genes for treating specific diseases. Many diseases are caused by abnormal levels of a specific gene, which can have harmful effects. Current technologies can overcompensate by delivering genes at extremely high levels, causing unwanted effects. This proposed technology aims to activate specific genes in the human genome in a controlled and reversible manner. By using the cell's own machinery, the proposed technology may precisely control gene expression to treat diseases where the molecule is delivered. If successful, the proposed technology may provide a new therapeutic approach for a variety of diseases, leading to better health outcomes for patients. In addition, the proposed technology may provide a new platform for drug development. This could lead to the development of new drugs for a wide range of diseases, improving quality of life for patients, and reducing healthcare costs.This I-Corps project is based on the development of a new genetic medicine platform that uses CRISPR/Cas-based epigenome editing to treat diseases by upregulating therapeutic genes. Current existing methods are not efficient at targeting specific non-coding regions of the genome. In contrast, the proposed technology is designed to target regions of the non-coding genome in human cells that are implicated in certain disease states and restore their function. In addition, the proposed technology enables the delivery of these molecules efficiently with reduced cytotoxicity and off-target effects while retaining function. This may overcome existing hurdles in delivering these therapies in vivo to reach higher levels of therapeutic targeting efficacy. The proposed technology has the potential to treat a variety of monogenic and complex diseases that previously were not accessible to current therapeutic approaches.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.