[Advances in AAV-CRISPR/Cas9-Mediated Hemophilia A Gene Therapy --Review].

Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.AAV-CRISPR/Cas9介导的血友病A基因治疗研究进展.血友病A是一种由凝血因子Ⅷ突变引起的X-连锁隐性出血性疾病。目前主要以外源凝血因子替代治疗为主。随着基因治疗的不断发展，为血友病A的治疗提供了新的研究方向。应用CRISPR-Cas9技术选择合适的靶位点，并通过相应的载体介导外源性B结构域删除的FⅧ变异体基因定向敲入和高效表达，达到治疗血友病A的目的。CRISPR-Cas9技术作为一种新兴的基因编辑工具，具有极大的高效性、安全性和有效性，已广泛用于血友病基因治疗研究。本文就现阶段血友病A基因治疗的载体选择、治疗基因的构建、基因编辑技术及表达靶位的选择进行综述。.