ABSTRACT
The complications in sickle cell anaemia result from the reduced solubility of deoxygenated sickle cell haemoglobin [HbS]. The sickling of the red cells is caused by the precipitation of haemoglobins as long, insoluble molecules. The finding that elevated fetal haemoglobin [HbF] levels inhibit the gelation of HbS and results in a benign state of the sickling disease, has initiated interest in drugs that 'switch on' the gamma-chain gene or 'turn off the beta-chain gene. 'Molecular therapy' of sickle cell anaemia is directed at either the inhibition of the gelation process, altering the gene or increasing haemoglobin oxygen affinity. Several substances have been tried in vitro and in vivo as inhibitors of sickling. 5-Azacytidine is one such drug but its use in vivo has been hindered as result of its toxic side-effects. The history of molecular therapy of sickle cell anaemia is outlined and the future is discussed