It is noteworthy that a lower on-target editing (and as a consequence a reduced off-target activity) achieved either by decreasing the exposure to the CRISPR-Cas9 (e.g., by reducing the RNP amount) or by using high-fidelity Cas9 could be envisaged, given the selective advantage of corrected RBCs in SCD patients,52,54 as shown for the Casgevy gene therapy.50 The gene discussed is RNPC3; the disease is Schnyder corneal dystrophy.