Evaluation of Cell-Penetrating Peptide Delivery of Antisense Oligonucleotides for Therapeutic Efficacy in Spinal Muscular Atrophy.
Evaluation of Cell-Penetrating Peptide Delivery of Antisense Oligonucleotides for Therapeutic Efficacy in Spinal Muscular Atrophy.
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DOI：
10.1007/978-1-4939-9670-4_13
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发表时间：
2019
影响因子：
--
通讯作者：
S. Hammond;F. Abendroth;M. Gait;M. Wood
中科院分区：
文献类型：
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作者：
S. Hammond;F. Abendroth;M. Gait;M. Wood
反义寡核苷酸(ASO)是一种广泛使用的基因治疗形式，可翻译为多种疾病。ASO疗效的一个主要障碍是其体内和体外研究的生物利用度。为了克服这一挑战，我们使用细胞穿透肽(CPPs)系统地递送ASOS。ASOS最先进的临床应用之一是治疗脊髓性肌萎缩症(SMA)。在这一章中，我们描述了用于体外筛选和分析针对存活运动神经元2的CPP偶联ASO的体内生物分布的技术，SMN是SMA的剂量依赖的修饰基因。
Antisense oligonucleotides (ASOs) are a widely used form of gene therapy, which is translatable to multiple disorders. A major obstacle for ASO efficacy is its bioavailability for in vivo and in vitro studies. To overcome this challenge we use cell-penetrating peptides (CPPs) for systemic delivery of ASOs. One of the most advanced clinical uses of ASOs is for the treatment of spinal muscular atrophy (SMA). In this chapter, we describe the techniques used for in vitro screening and analysing in vivo biodistribution of CPP-conjugated ASOs targeting the survival motor neuron 2,SMN2, the dose-dependent modifying gene for SMA.