Current Therapies in Hemophilia: From Plasma-Derived Factor Modalities to CRISPR/Cas Alternatives

Review

Current Therapies in Hemophilia: From Plasma-Derived Factor Modalities to CRISPR/Cas Alternatives

Irving Jair Lara-Navarro^1,2 and Ana Rebeca Jaloma-Cruz¹

¹División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México
²Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México

Since the middle of the last century, there have been amazing therapeutic advances for hemophilia such as the development of plasma-derived products and bioengineered recombinant factors VIII and IX (for hemophilia A and B, respectively) with improved stability, higher activity, and extended half-life. The recent use of a monoclonal antibody that mimics factor VIII activity (which is an efficient treatment for all hemophilia A phenotypes with or without inhibitors) has shown the great possibilities of non-factor therapies for improving the quality of life of hemophilia A patients, with a safer application and long-lasting effects. Gene therapy offers the promise of a “true cure” for hemophilia based on the permanent effect that a gene edition may render. Clinical trials developed in the last decade based on adenoviral vectors show modest but consistent results; now, CRISPR/Cas technology (which is considered the most efficient tool for gene edition) is being developed on different hemophilia models. Once the off-target risks are solved and an efficient switch on/off for Cas activity is developed, this strategy might become the most feasible option for gene therapy in hemophilia and other monogenic diseases.

Keywords —— CRISPR/Cas; gene therapy; hemophilia; prophylactic management; protein substitution therapy

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Tohoku J. Exp. Med 2022, 256, 197-207.

Correspondence: Ana Rebeca Jaloma-Cruz, División de Genótica, Centro de Investigación Biomódica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Col. Independencia, Guadalajara, Jalisco 44340, Móxico.

e-mail: arjaloma@gmail.com