Abstract

GENE THERAPY IN HEMOPHILIA

*Sukanya Garje, Kalpana S. Kale and Dr. Megha Salve

Abstract

Hemophilia is a genetic mutation disorder that impacts the coagulation factor VIII or factor IX genes. The preferred palliative treatment is based on the application of safe and effective recombinant coagulation factors. So far, the results have been promising regarding the levels and timing of expression, primarily utilizing adeno-associated vectors. Nonetheless, these treatments are linked to immunogenicity and liver toxicity. Vector serotypes and transgenes (variants) improve coagulation efficiency, thereby increasing the success of these protocols. It's crucial for both doctors and patients to understand the possible advantages and dangers of the new treatments, and a registry of gene therapy patients should be maintained, containing details on the effectiveness and long-term negative effects related to the therapies given. In the field of hemophilia, gene therapy can lead to reduced costs (especially indirect) and promote a more equitable distribution of treatments. For hemophilia A, additional studies are required to determine the best methods for effectively packing the sizable factor VIII gene into the vector. In contrast, for hemophilia B, the focus should be on enhancing both the vector serotype to lower its immunogenicity and hepatotoxicity, as well as the transgene to improve its clotting effectiveness. This approach aims to reduce the total amount of vector used and lower the frequency of adverse events without affecting the protein's expressed efficacy.

Keywords: Hemophilia; gene therapy; immune tolerance induction; viral vectors; CRISP -Cas-9; bispecific antibodies; AAV.