Box 1 Gene therapy treatment

Gene therapy has been researched for decades and is assumed to be a one-time treatment in which genetic material coding for the deficient protein is inserted in the nucleus of targeted cells, giving those cells the ability to produce that protein [16, 19]. Several approaches for delivery of the genetic material are applied which can be broadly categorized into in vivo and ex vivo [20, 21]

In the in vivo approach, specific tissues are targeted by using a virus as a vector [20, 21]. This is a relatively simple procedure. However, it might be that the virus used as a vector can only be used once in an individual because the immune system will recognize it a second time

The ex vivo approach is more elaborate and requires hematopoietic stem cells to be recruited from the patient and to be transduced with the correct DNA in vitro. The patient receives chemotherapy to clear residual hematopoietic stem cells, after which the transduced stem cells are reintroduced [20, 21]

Effectiveness depends on the ability of the transduced cells to release the enzyme into the circulation and whether the enzyme is then able to reach affected tissues. Long term effects of both approaches have not been extensively researched. Development of neutralizing antibodies and/or immune reactions might influence the long term treatment effects [22]