CAGT/PGC Seminar: Fyodor Urnov, PhD

The vast majority of diseases clinically tractable by genome editing using current-state technology are not the targets of active preclinical or clinical development. Addressing this issue will require more involvement of the academic/nonprofit sector, but despite an existing charted path for advancing genome editing of specific cell types and tissues (such as T cells, hematopoietic stem cells, the liver, and the retina) to the clinic, there presently is only one open US IND for genome editing by an all-academic group. A key reason is that the current manufacturing, regulatory, and healthcare economics environment is not configured to maximize clinical impact of a technology like CRISPR-Cas. Under the framework that exists today, a pediatric patient newly diagnosed with a terminal illness such as a severe inborn error of immunity due to a never-before-seen but clinically editable mutation and a life expectancy of < 1 yr will have to wait ~3.5 years until a gene editing medicine is engineered, tested, and manufactured at an approximate total cost of $9m. An actionable path through this status quo is to develop and clinically derisk a dedicated nonclinical development path for use in academic/nonprofit settings in N=1/rare situations of dire medical need. From a technology standpoint, this will require comprehensive leveraging of the intrinsically platform nature of CRISPR-Cas gene editing. The Innovative Genomics Institute in close partnership with clinicians at UCSF and UCLA is developing such a platform focused on inborn errors of immunity, where ca 112,000 known patients suffering from 505 currently known diseases lack even a single open trial for genome editing open at the present time.