Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients
G Lacerra, H Sierakowska, C Carestia… - Proceedings of the …, 2000 - National Acad Sciences
G Lacerra, H Sierakowska, C Carestia, S Fucharoen, J Summerton, D Weller, R Kole
Proceedings of the National Academy of Sciences, 2000•National Acad SciencesMononuclear cells from peripheral blood of thalassemic patients were treated with
morpholino oligonucleotides antisense to aberrant splice sites in mutant β-globin precursor
mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of β-
globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients
with IVS2–654/βE, IVS2–745/IVS2–745, and IVS2–745/IVS2–1 genotypes. The maximal Hb
A level for repaired IVS2–745 mutation was≈ 30% of normal; Hb A was still detectable 9 …
morpholino oligonucleotides antisense to aberrant splice sites in mutant β-globin precursor
mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of β-
globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients
with IVS2–654/βE, IVS2–745/IVS2–745, and IVS2–745/IVS2–1 genotypes. The maximal Hb
A level for repaired IVS2–745 mutation was≈ 30% of normal; Hb A was still detectable 9 …
Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant β-globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of β-globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2–654/βE, IVS2–745/IVS2–745, and IVS2–745/IVS2–1 genotypes. The maximal Hb A level for repaired IVS2–745 mutation was ≈30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective β-globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.
National Acad Sciences