División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social.
Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.
Tohoku J Exp Med. 2022 Mar;256(3):197-207. doi: 10.1620/tjem.256.197.
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.
自上世纪中叶以来，血友病的治疗取得了令人瞩目的进展，例如开发了血浆衍生产品和生物工程重组因子 VIII 和 IX（分别用于治疗血友病 A 和 B），这些产品具有更好的稳定性、更高的活性和更长的半衰期。最近使用一种模拟因子 VIII 活性的单克隆抗体（这是一种有效治疗所有血友病 A 表型的方法，无论是否存在抑制剂），表明非因子治疗在提高血友病 A 患者生活质量方面具有巨大的潜力，其应用更安全，效果更持久。基因治疗基于基因编辑可能产生的永久效果，有望为血友病提供“真正的治愈”。过去十年基于腺病毒载体开发的临床试验显示出适度但一致的结果；现在，CRISPR/Cas 技术（被认为是基因编辑最有效的工具）正在不同的血友病模型上开发。一旦解决了脱靶风险并开发出有效的 Cas 活性开关，该策略可能成为血友病和其他单基因疾病基因治疗最可行的选择。
