Induced dystrophin exon skipping in human muscle explants
Induced dystrophin exon skipping in human muscle explants
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DOI：
10.1016/j.nmd.2006.05.017
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发表时间：
2006-10-01
影响因子：
2.8
通讯作者：
Wilton, S. D.
中科院分区：
文献类型：
--
作者：
McClorey, G.;Fall, A. M.;Wilton, S. D.
反义寡核苷酸（AO）操纵前mRNA剪接的肌营养不良蛋白基因是克服杜氏肌营养不良症（DMD）引起的突变的希望。迄今为止，这种方法仅限于使用动物模型或培养的人类肌肉细胞的研究，并且尚未显示AO可以诱导人类肌肉中的外显子跳跃的证据。在这项研究中，我们使用不同的AO类似物诱导外显子跳跃肌肉外植体来自正常和DMD的人组织。我们提出，在人类肌肉外植体中诱导外显子跳跃比单层培养中的细胞更接近体内条件，并且可以最大限度地减少I期临床研究中的参与者数量，以证明人类肌肉中外显子跳跃的原理。(C)2006 Elsevier B.V.保留所有权利。
Antisense oligonucleotide (AO) manipulation of pre-mRNA splicing of the dystrophin gene is showing promise in overcoming Duchenne muscular dystrophy (DMD)-causing mutations. To date, this approach has been limited to studies using animal models or cultured human muscle cells, and evidence that AOs can induce exon skipping in human muscle has yet to be shown. In this study, we used different AO analogues to induce exon skipping in muscle explants derived from normal and DMD human tissue. We propose that inducing exon skipping in human muscle explants is closer to in vivo conditions than cells in monolayer cultures, and may minimize the numbers of participants in Phase I clinical studies to demonstrate proof of principle of exon skipping in human muscle. (C) 2006 Elsevier B.V. All rights reserved.