Give Cas a Chance: An Actionable Path to a Platform for CRISPR Cures

The field of clinical gene editing has a bona fide crisis on its hands—a crisis that has to, and can be, promptly resolved.

An outside observer of our field might be surprised by this and say—what crisis? The first gene-editing medicine, Casgevy,¹ was approved less than 12 months ago. The clinical trial efficacy and safety data supporting this approval are spectacular.^2,3Significantly, Casgevy is indicated for the two most common Mendelian disorders on Earth, sickle cell disease and transfusion-dependent β-thalassemia. At the same time, gene editing has advanced to two phase 3 clinical trials, one of which, for transthyretin (TTR) amyloidosis, is enrolling 765 subjects;⁴ this is based on equally spectacular phase 1/2 data for safety, tolerability, and durability of effect on an efficacy biomarker.⁵ Further, results of a PubMed search for “CRISPR or Cas9” resemble the Amazon rainforest with its rich ecosystem of publications describing not only nonclinical data of efficacy for gene-editing treatment of various diseases, but discoveries of new enzymes to drive gene editing, new methods to derisk them, and...