Duan Dongsheng
Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO 65212, USA; Department of Neurology, School of Medicine, The University of Missouri, Columbia, MO 65212, USA; Department of Bioengineering, The University of Missouri, Columbia, MO 65212, USA; Department of Biomedical Sciences, College of Veterinary Medicine, The University of Missouri, Columbia, MO 65212, USA.
Curr Opin Virol. 2016 Dec;21:16-25. doi: 10.1016/j.coviro.2016.07.006. Epub 2016 Jul 25.
For diseases like muscular dystrophy, an effective gene therapy requires bodywide correction. Systemic viral vector delivery has been attempted since early 1990s. Yet a true success was not achieved until mid-2000 when adeno-associated virus (AAV) serotype-6, 8 and 9 were found to result in global muscle transduction in rodents following intravenous injection. The simplicity of the technique immediately attracts attention. Marvelous whole body amelioration has been achieved in rodent models of many diseases. Scale-up in large mammals also shows promising results. Importantly, the first systemic AAV-9 therapy was initiated in patients in April 2014. Recent studies have now begun to reveal molecular underpinnings of systemic AAV delivery and to engineer new AAV capsids with superior properties for systemic gene therapy.
对于像肌肉萎缩症这样的疾病，有效的基因治疗需要在全身范围内进行矫正。自20世纪90年代初以来，人们就尝试通过全身递送病毒载体来实现这一目标。然而，直到2000年年中，当腺相关病毒（AAV）血清型6、8和9被发现经静脉注射后能在啮齿动物体内实现全身肌肉转导时，才取得了真正的成功。该技术的简便性立刻引起了人们的关注。在许多疾病的啮齿动物模型中，已经实现了令人惊叹的全身改善效果。在大型哺乳动物中扩大规模的研究也显示出了有前景的结果。重要的是，首例全身性AAV-9治疗于2014年4月在患者中启动。最近的研究现已开始揭示全身性AAV递送的分子基础，并设计出具有更优特性的新型AAV衣壳用于全身性基因治疗。
