[jfarlow]

Ultimately, they are delivering a payload with a slightly modified version of wild-type hemoglobin (a single point mutation from wild-type). Patients with sickle-cell disease have a (different) mutation in their hemoglobin that causes the hemoglobin protein to aggregate, and not carry oxygen. The modified version being delivered to patients is not just a 'corrected, wild-type' version of the protein capable of carrying oxygen more efficiently, but actually carries a synthetic mutation that actually prevents the patient's version from aggregating. So if even 20% of the hemoglobin in the treated patient's blood is of this modified type, then none of their hemoglobin will aggregate, and they should get much of their oxygen-carrying capacity back. This modification to the introduced version of the protein also allows it to be easily identified and tracked to monitor things like its concentration.

The actual sequence and mutation HBB [T87Q] protein: https://serotiny.bio/pinecone/part/10803

A short little writeup I did about the mutation: https://serotiny.bio/notes/proteins/hbb/

A very detailed presentation about Bluebird Bio's therapy (called LentiGlobin BB305) provided to the government: (PDF warning) http://osp.od.nih.gov/sites/default/files/1164_bluebirdbio.p...