I-Corps: Targeted Epigenetic Modulation to Activate Therapeutic Genes

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.