Exploiting epigenetics for the treatment of inborn errors of metabolism
Exploiting epigenetics for the treatment of inborn errors of metabolism
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DOI：
10.1002/jimd.12093
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发表时间：
2020-01-01
影响因子：
4.2
通讯作者：
Oosterveer, Maaike H.
中科院分区：
文献类型：
--
作者：
Rutten, Martijn G. S.;Rots, Marianne G.;Oosterveer, Maaike H.
基因疗法目前被认为是先天性代谢错误（IEM）的最佳治疗方法，因为它的目的是永久补偿原发性遗传缺陷。然而，新兴的基因编辑方法，如 CRISPR-Cas9，可以在精确的位置编辑宿主生物体的 DNA，可能具有超越治疗的潜力。基因编辑策略旨在纠正实际的基因突变，同时规避与传统补偿基因疗法相关的问题。这些策略还可以重新调整用途，使继发于遗传缺陷的基因表达变化正常化。此外，除了 IEM 的遗传原因外，人们越来越认识到它们的临床表型与表观遗传变化有关。由于表观遗传改变基本上是可逆的，这可能为 IEM 患者的治疗提供新的机会。在这里，我们概述了表观遗传学在最终治疗 IEM 中的前景。我们讨论基因和表观遗传编辑的概念，以及当前和即将推出的基于基因的 IEM 疗法的优点和缺点。
Gene therapy is currently considered as the optimal treatment for inborn errors of metabolism (IEMs), as it aims to permanently compensate for the primary genetic defect. However, emerging gene editing approaches such as CRISPR-Cas9, in which the DNA of the host organism is edited at a precise location, may have outperforming therapeutic potential. Gene editing strategies aim to correct the actual genetic mutation, while circumventing issues associated with conventional compensation gene therapy. Such strategies can also be repurposed to normalize gene expression changes that occur secondary to the genetic defect. Moreover, besides the genetic causes of IEMs, it is increasingly recognized that their clinical phenotypes are associated with epigenetic changes. Because epigenetic alterations are principally reversible, this may offer new opportunities for treatment of IEM patients. Here, we present an overview of the promises of epigenetics in eventually treating IEMs. We discuss the concepts of gene and epigenetic editing, and the advantages and disadvantages of current and upcoming gene-based therapies for treatment of IEMs.