The latest CRISPR base-editing trials for sickle cell are showing durable correction at the HBB locus more than two years out, with no detectable off-target edits in the highest-coverage long-read screens. Casgevy was the proof of concept; the next-gen ABEs are quieter and don't require the double-strand break. The ethics around germline are still a hard line, but somatic therapy for monogenic blood disorders is genuinely working now.