sickle cell hemoglobin :
sickle cell hemoglobin the most common hemoglobin type is a tetramer (which contains 4 subunit proteins)
In adult humans, called hemoglobin A, consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively
As an infant, the hemoglobin molecule is made up of 2 α chains and 2 gamma chains. The gamma chains are gradually replaced by β chains as the infant grows.
Slide 4:
SCD became the first genetic
disorder for which a causative mutation was identified at the molecular level: the substitution of valine for glutamic acid in human β A globin codon 6 .
In homozygotes, the abnormal
hemoglobin (Hb) [HbS (α2β2S)] polymerizes in long fibers upon deoxygenation within red blood cells (RBCs), which become deformed (“sickled”), rigid, and adhesive, thereby triggering microcirculation occlusion, anemia, infarction, and organ damage.
Slide 5:
γ- globin – inhibits polymerisation
Lentiviral vectors : They have recently been adapted as gene delivery vehicles (vectors) thanks to their ability to integrate into the genome of non-dividing cells, which is the unique feature of Lentiviruses as other Retroviruses can infect only dividing cells
Slide 6:
They constructed a human β A-globin gene variant mutated at codon 87 to encode the amino-acid residue believed to be responsible for most of the antisickling activity of γ-globin
[β A87 Thr:Gln (β A-T87Q)].