The protein, HBB [T87Q] is a single point mutation of the wild-type human hemoglobin, HBB that confirs a cure to patients with Sickle-cell disease. The disease is caused by a patient having a variation of their wild-type HBB protein that aggregates instead of performing its duties as an oxygen carrier.

Therapeutically, if the wild-type HBB were delivered to a person with sickle cell disease, the new protein could only dilute protein aggregation that would already occur. However the engineered [T87Q] mutation actually inhibits the polymerization of hemoglobin associated with sickle cell disease. If as little as 20% of the overall hemoglobin content contains the [T87Q] mutation, the rest does not seem to polymerize.

Clinically the mutation also serves the purpose of being ‘different’ than the wild-type version of hemoglobin so that it is possible to measure how much of this new protein is being made (and evaluate the treatment).

Identification of HBB, mutations associated with sickle cell disease and mutations associated with inhibiting polymerization were discovered in the mid 1980s. In the early 2000s mice were able to be cured using gene therapies. Clinical trials began in the late 2000s, and multiple gene therapy trials are in patients today in France, Thailand, Australia and the United States.1 These trials using the [T87Q] variant of HBB are being conducted by Bluebird Bio.