A Hemophilia Disorder Review: Gene Therapy for Hemophilia B Treatment using rAAV vectors

Abstract

Hemophilia is an X-linked recessive disorder characterized by the deficiency in one protein essential for blood coagulation. There are two main types of variants of this disease; hemophilia A (HA) which is related with blood clotting factor VIII (FVIII) deficiency and hemophilia B (HB) which is related with factor IX (FIX) deficiency. Nowadays, there are several options to treat this disorder, however, the most efficient is gene therapy since it has a long-term effect, and contrasts with traditional methods. This review is focused on hemophilia B treatment because FIX is a smaller protein than FVIII (<1kb), and thereby is easier to study. Within gene therapy, methods which use recombinant adeno-associated virus (rAAV) vectors are the best alternative to treat HB since they are safe and reliable. Moreover, rAAV vectors have the advantage of having a low inflammatory potential, a non-pathogenic status, plus the potential for long-term expression of the transferred gene. However, some patients showed an immune response to the capsids of the vectors before treatment. Hence, possible solutions were needed; one of them being the use of anti-antibodies. Finally, clinical trials results showed that under the use of the optimized codon hFIXco and serotype 8 the levels of expression were persistent, demonstrating the potential of gene therapy for hemophilia B treatment.