Author:
Worth Eli H.,Fugate Mark K.,Grasty Kimberly C.,Loll Patrick J.,Bishop Marilyn F.,Ferrone Frank A.
Abstract
AbstractAdults with sickle cell disease bear a mutation in the β-globin gene, leading to the expression of sickle hemoglobin (HbS; α2βS2). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, α2γ2); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ chain or introduce a gene encoding a modified β chain having γ-like character. Here, we show that a single-site modification on the α chain, αPro114Arg, retards fiber formation as effectively as HbF. Because this addition to the repertoire of anti-sickling approaches acts independently of other modifications, it could be coupled with other therapies to significantly enhance their effectiveness.
Funder
Commonwealth of Pennsylvania CURE program
Publisher
Springer Science and Business Media LLC