Imagine CRISPR cures

A decade of progress in sequencing and in CRISPR/Cas technologies has created a situation without precedent in the history of medicine. Starting with an individual patient, next-generation sequencing can diagnose, in less than 24 h, the genetic basis of a Mendelian disorder.¹ Once the causative mutation is found, CRISPR/Cas, in principle, represents a targeted therapy, a first-pass iteration of which can be designed in silico within minutes thanks to straightforward principles of target locus recognition by Cas9.² The juxtaposition of the two to yield a treatment is not a hypothetical. For Mendelian disorders of hematopoiesis and those that can be treated by editing genes in the liver or the eye, a charted path exists to (1) engineer a CRISPR/Cas-based therapeutic, (2) complete IND-enabling preclinical safety, efficacy, and manufacturing studies, and (3) perform a phase 1/2 clinical trial. Three ongoing such trials have reduced all of this to practice,^3,4 with a good safety record in ∼22 (sickle cell disease and transfusion-dependent β-thalassemia), 6 (TTR amyloidosis), and 6 (Leber's congenital amauropathy) subjects dosed to date; in the first case, all subjects for whom... see more