Gene Therapy in Hemophilia: Recent Advances

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defecti...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (14), p.7647
Main Authors: Rodríguez-Merchán, E. Carlos, De Pablo-Moreno, Juan Andres, Liras, Antonio
Format: Article
Language:English
Subjects:
Clotting
Coagulation
Coagulation factor VIII
Coagulation factors
Disease prevention
Drug dosages
Expression vectors
Factor IX deficiency
Gene expression
Gene therapy
Genetic engineering
Hemophilia
Hepatotoxicity
Immunogenicity
Monoclonal antibodies
Patients
Physicians
Proteins
Review
Serotypes
Stem cells
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Summary:Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22147647