Winkelsas Audrey M, Fischbeck Kenneth H
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Curr Opin Genet Dev. 2020 Dec;65:112-116. doi: 10.1016/j.gde.2020.05.022. Epub 2020 Jul 2.
Nucleic acid therapeutics allow sequence-based targeting of mutation-harboring genes. They can be used to increase the expression and function of disease genes or to decrease the expression of toxic gene products. Antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and gene-replacement therapies have received FDA approval, and in vivo gene editing applications are currently under development. Special consideration should be given to target engagement in neurons and amelioration of neurological phenotypes. Here we discuss the uses and limitations of different nucleic acid therapeutics, highlighting examples in the clinical and pre-clinical application of these modalities for the treatment of neurodevelopmental diseases.
核酸疗法能够对携带突变的基因进行基于序列的靶向作用。它们可用于增加疾病基因的表达和功能，或降低有毒基因产物的表达。反义寡核苷酸（ASO）、小干扰RNA（siRNA）和基因替代疗法已获得美国食品药品监督管理局（FDA）的批准，体内基因编辑应用目前也正在开发中。应特别考虑在神经元中的靶点结合以及神经表型的改善。在此，我们讨论不同核酸疗法的用途和局限性，重点介绍这些疗法在治疗神经发育疾病的临床和临床前应用中的实例。
