Gene Therapy for Haemophilia B - Kyle Wong
Famous for its inheritance down the royal bloodlines of Queen Victoria, Haemophilia B has long since remained an incurable genetic disease (D.J. Roberts 2012).
Haemophilia occurs when sufferers have a damaged gene which causes its sufferers to not produce Factor IX, a plasma coagulation protein which stops bleeding in normal human beings. Haemophiliacs suffer from excessive bleeding due to their blood being unable to clot properly. Imagine that! They could quite literally die from something as small as a papercut. Up until now, this disease has been treated by the injection of the coagulation factors and recombinant proteins when a bleed occurs in order to cause the wounds to clot. (PubMed 2010)
This process however is prophylactic, that is it a preventative, protective measure, rather than a viable cure (Nathwani et al 2011). Now what happens is that those who donate blood have their blood separated by centrifugation, and from the plasma, products with Factor IX can be made and given to haemophiliacs.
There are two main problems with the status quo of treating Haemophilia B patients:
- 1. The process has to occur regularly, 2-3 times a week. The estimated cost of the procedure for just one year is roughly $300,000 (Wade 2011)
- 2. There is a chance that disease can be transmitted from the donors to the recipients via the donated plasma.
However, a new gene therapy procedure has been developed that can replace the defective genes and effectively cure haemophiliacs.
What is Gene Therapy? Gene therapy involves the extraction of a defective gene in the DNA and replacing it with the correct form, through the use of a vector, a way for the gene to be transported into the cells (Wade 2011)
Previously, gene therapy had remained relatively ineffective because the body would destroy the virus vector before it could deliver the gene. But here’s where the scientists have been able to do something really cool. Scientists have been able to manipulate virus vector in a way which limits the chances of the body having a negative immune response. Scientists have been able to encourage the positive reception of the gene by doing four things:
- 1. Treating the patients with steroids that supress the immune system and lower the chances of an immune response
- 2. Enhancing the expression of Factor IX through a process called codon optimization
- 3. Pseudotyping the adenovirus-associated virus vector, meaning the virus is combined with a foreign viral membrane with specific glycoproteins that will bind to liver cells
- 4. Injection of viral vector into the peripheral vein of the body, allowing access to the liver (Nathwani et al. 2011)
Once injected into the body, the virus targets the liver cells where Factor IX is normally produced. The viral envelope merges with the cell membrane releasing its contents into the cell. The correct form of the gene enters the cell’s nucleus and combines with the genetic material. The patient is then able to produce Factor IX (Nathwani et al. 2011).