Gene Therapy for Inherited Bleeding Disorders.
Gene Therapy for Inherited Bleeding Disorders.
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遗传性出血性疾病的基因治疗。
DOI：
10.1055/s-0041-1722862
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发表时间：
2021-03
影响因子：
5.7
通讯作者：
Samelson-Jones BJ
中科院分区：
文献类型：
--
作者：
Arruda VR;Weber J;Samelson-Jones BJ
数十年来，血友病基因治疗的临床前和临床研究即将取得成果，目前有希望的关键研究可能会获得监管部门的批准。然而，最近的成功不应掩盖为达到这一目标所克服的多重挑战。血友病A和B的基因治疗受益于一般基因领域的进步，如腺相关病毒载体的发展，以及疾病特异性的突破，如B结构域缺失因子VIII和多活性因子IX Padua的鉴定。基因治疗领域也受益于血友病B临床研究，这些研究首次揭示了与载体衣壳免疫反应相关的关键安全性问题，而这些问题在临床前模型中没有预料到。临床前研究还研究了其他罕见遗传性出血性疾病的基因转移方法，包括因子7缺乏症、血管性血友病和格兰兹曼血栓缺乏症。在这里，我们回顾了血友病基因治疗的成功历程，并提出了一些悬而未决的问题。然后，我们讨论了基因治疗这些其他罕见的遗传性出血性疾病的现状，以及血友病基因治疗的经验教训如何指导临床发展。
Decades of preclinical and clinical studies developing gene therapy for hemophilia are poised to bear fruit with current promising pivotal studies likely to lead to regulatory approval. However, this recent success should not obscure the multiple challenges that were overcome to reach this destination. Gene therapy for hemophilia A and B benefited from advancements in the general gene ther field, such as the development of adeno-associated viral vectors, as well as disease-specific breakthroughs, like the identification of B-domain deleted factor VIII and hyperactivefactor IX Padua. The gene therapy field has also benefited from hemophilia B clinical studies, which revealed for the first time critical safety concerns related to immune responses to the vector capsid not anticipated in preclinical models. Preclinical studies have also investigated gene transfer approaches for other rare inherited bleeding disorders, including factor VII deficiency, von Willebrand disease, and Glanzmann thrombasthenia. Here we review the successful gene therapy journey for hemophilia and pose some unanswered questions. We then discuss the current state of gene therapy for these other rare inherited bleeding disorders and how the lessons of hemophilia gene therapy may guide clinical development.
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影响因子：
20.3
作者：
Crudele, Julie M.;Finn, Jonathan D.;Arruda, Valder R.
通讯作者：
Arruda, Valder R.
影响因子：
17.1
作者：
Cantore, Alessio;Ranzani, Marco;Naldini, Luigi
通讯作者：
Naldini, Luigi
影响因子：
20.3
作者：
Fahs, Scot A.;Hille, Matthew T.;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
DOI：
10.1161/atvbaha.108.168369
发表时间：
2008-09-01
影响因子：
8.7
作者：
De Meyer, Simon F.;Vandeputte, Nele;Vanhoorelbeke, Karen
通讯作者：
Vanhoorelbeke, Karen
影响因子：
20.3
作者：
Arruda, VR;Hagstrom, JN;High, KA
通讯作者：
High, KA