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Genome editing using CRISPR-Cas9 has produced a functional cure for a small number of patients with sickle cell disease and beta-thalassemia. Rather than repairing the causative mutation, this striking outcome was attained by the knockout of a lineage-specific regulatory element for a gene, BCL11A, that controls fetal hemoglobin levels: a first example of clinical success in targeting a locus initially identified in a genome-wide association study, and formal proof of the "in the age of CRISPR, the entire genome is a druggable target" notion. This remarkable development, along with advancement to the clinic of several additional editing-based approaches to the hemoglobinopathies, highlights a sense of urgency in accelerating scientific, regulatory, and public health innovation that will allow broad and equitable access to editing-based cures.

Genome editing with engineered nucleases, a powerful tool for understanding biological function and revealing causality, was built in a joint effort by academia and industry in 1994-2010. Use of CRISPR-Cas9 is the most recent (2013-), and facile, implementation of the resulting editing toolbox. Principles and methods of genome editing from the pre-CRISPR era remain relevant and continue to be useful.