Gene therapy as an innovative approach to the treatment of hemophilia B-a review

Abstract

Hemophilia B is a disease that affects the human coagulation system, causing the absence or deficiency of coagulation factor IX, which may manifest itself in uncontrolled bleeding that is life-threatening to patients. Due to its inheritance, the disease more often affects men, and the severity of symptoms directly correlates with the concentration of the missing factor IX; hence, the aim of therapy is to maintain it at a level that allows for sufficient hemostasis. The basic model of treatment offered to patients is based on primary prevention with coagulation factor IX with a prolonged half-life, which, however, does not solve the numerous problems faced by patients. An innovative proposal that, despite initial concerns, is becoming more and more popular every day is the recently approved genetic therapy in Europe, which uses viral vectors to transfer the correct gene that encodes coagulation factor IX. The introduction of a recombinant gene in place of its defective counterpart seems to be a promising solution and the beginning of a new era in which genetic therapies have a chance to develop their full potential and replace existing therapeutic regimens.

Keywords: Etranacogene dezaparvovec; Gene therapy; Hemophilia B; Viral vectors.

Fig. 1

A timeline of milestones in the development of hemophilia B treatment

Fig. 2

Naturally occurring adenovirus consists of two open reading frames—rep and cap, flanked by ITR sequences. The rep and cap sequences are removed from the wtAAV virus DNA and replaced with a transgene consisting of the gene of interest—gene of factor IX, other transcription regulatory sequences—polyA and promoter. Eventually the AAV vector consists of a recombinant AAV genome and capsid, showing tropism to the hepatocytes