Hollinger Katrin, Chamberlain Jeffrey S
Department of Neurology, Wellstone Muscular Dystrophy Research Center, University of Washington School of Medicine, Seattle, Washington, USA.
Curr Opin Neurol. 2015 Oct;28(5):522-7. doi: 10.1097/WCO.0000000000000241.
Gene therapy as a treatment for neuromuscular disease has significantly advanced over the past decade. In the present review, the progress of adeno-associated viruses (AAV) vector-mediated gene therapy for Duchenne muscular dystrophy (DMD) during the past year is highlighted.
Modulating the immune response to AAV vector capsid or the transgene has helped to increase stable transduction efficiency. Full-length dystrophin expression via gene editing with targeted nucleases may ultimately be an ideal treatment option. Also genes with homologues function may ameliorate many aspects of the DMD pathophysiology.
The work during the past year has increased our understanding of AAV vector-mediated therapy and has also validated new approaches to treat DMD. The results will aid in the design of both preclinical and clinical trials.
在过去十年中,基因治疗作为治疗神经肌肉疾病的方法取得了显著进展。在本综述中,重点介绍了过去一年腺相关病毒(AAV)载体介导的杜氏肌营养不良症(DMD)基因治疗的进展。
调节对AAV载体衣壳或转基因的免疫反应有助于提高稳定的转导效率。通过使用靶向核酸酶进行基因编辑实现全长肌营养不良蛋白表达最终可能是一种理想的治疗选择。此外,具有同源功能的基因可能改善DMD病理生理学的许多方面。
过去一年的工作增进了我们对AAV载体介导治疗的理解,也验证了治疗DMD的新方法。这些结果将有助于临床前和临床试验的设计。