Abstract

Evidence from multiple ongoing clinical trials proves that genome editing can attain robust disease-modifying outcomes in multiple indications including sickle cell disease, transfusion-dependent beta-thalassemia, and TTR amyloidosis. Current regulatory and manufacturing frameworks, however, are not scaled to expand the clinical footprint of CRISPR to a substantial fraction of Mendelian disease, even in settings where a charted path exists to advance editing to the clinic (such as inborn errors of immunity). Such an expansion will require the engineering and clinical development of a fundamentally new approach to designing, developing, and deploying CRISPR-based genomic medicines. The academic/nonprofit sector is a key venue for this effort, with nonmalignant hematology as an actionable disease space for reducing such an approach to practice in the next 3-5 years.