Haemophilias: advances towards genetic engineering replacement therapy

Both haemophilia A and B are X-linked recessive disorders and therefore occ ur almost exclusively in males, The genes for both factors VIII and IX have been mapped to the distal end of the long arm of the X chromosome, bands X q28 and Xq27.1, respectively. The Factor VIII gene comprises 186kb DNA with 9 kb of exon of DNA which encodes an mRNA of nearly 9 kb, The Factor IX ge ne is 34 kb in length and the essential genetic information is present in e ight exons which encode 1.6kb mRNA. in gene therapy, genetic modification o f the target cells can be either ex: vivo or in vivo. The advantage of the ex vivo approach is that the genetic modification is strictly limited to th e isolated cells, In the in vivo approach, the integrity of the target tiss ue is maintained but the major challenge is to deliver the gene to the targ et tissue. The use of improved retroviral and adenovirus-based vectors for gene therapy has produced clinically relevant levels of human factor VIII i n mice and haemophilic dogs. If further improvements can increase the persi stence of expression and decrease the immunological responses, phase I clin ical trials in patients can be considered.