NIH R01 · 2025
Fundamentals of Anti-Sickling Therapies
Sickle cell disease affects 100,000 Americans and millions world-wide: a mutation in the β-globin gene gives rise to a hemoglobin variant (sickle hemoglobin, or HbS) that is prone to self-assembly. The resulting protein fibers distort red blood cells and cause the disease’s pathology. Two gene therapies have recently been approved for treatment of this disorder; both are based on the observation that co-expression of fetal hemoglobin (HbF) reduces the formation of sickle fibers. However, we lack a mechanistic understanding of how HbF achieves its anti-sickling effects; simple models in which HbF is suggested to reduce fiber nucleation by diluting HbS fail to explain HbF’s observed actions.…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.