Beyond “One disease at a time”: Therapeutic platforms for rare monogenic disease

Based on the most recent estimates, there are over 10,000 known human diseases, and more are being discovered each day. A large fraction of these are rare monogenic (Mendelian) disorders. Gene-targeted therapies, such as gene therapy, gene editing, and oligonucleotides are therapeutic platforms that are broadly applicable to a large fraction of monogenic diseases. However, these technologies are currently developed as treatments for one disease at a time. This approach favors the most common rare diseases, and will leave many diseases and patients who could greatly benefit from gene targeted therapies behind. To address this disparity, a fundamentally different way of thinking about the problem is required. One potential solution, based on the science itself, is to develop gene-targeted therapies as therapeutic platforms to treat monogenic disease, rather than as treatments for one disease at a time. I will discuss the implications and challenges of this approach and provide examples of ongoing research in this area. See pave-gt.ncats.nih.gov ; fnih.org/our-programs/AMP/BGTC ; commonfund.nih.gov/editing .