医学
反义治疗
杜氏肌营养不良
脊髓性肌萎缩
转甲状腺素
肌萎缩侧索硬化
神经学
寡核苷酸
生物信息学
药理学
疾病
内科学
DNA
生物
遗传学
精神科
锁核酸
作者
Man Amanat,Christina L. Nemeth,Amena Smith Fine,Doris Leung,Ali Fatemi
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2022-11-05
卷期号:14 (11): 2389-2389
被引量:10
标识
DOI:10.3390/pharmaceutics14112389
摘要
Antisense oligonucleotides (ASOs) are disease-modifying agents affecting protein-coding and noncoding ribonucleic acids. Depending on the chemical modification and the location of hybridization, ASOs are able to reduce the level of toxic proteins, increase the level of functional protein, or modify the structure of impaired protein to improve function. There are multiple challenges in delivering ASOs to their site of action. Chemical modifications in the phosphodiester bond, nucleotide sugar, and nucleobase can increase structural thermodynamic stability and prevent ASO degradation. Furthermore, different particles, including viral vectors, conjugated peptides, conjugated antibodies, and nanocarriers, may improve ASO delivery. To date, six ASOs have been approved by the US Food and Drug Administration (FDA) in three neurological disorders: spinal muscular atrophy, Duchenne muscular dystrophy, and polyneuropathy caused by hereditary transthyretin amyloidosis. Ongoing preclinical and clinical studies are assessing the safety and efficacy of ASOs in multiple genetic and acquired neurological conditions. The current review provides an update on underlying mechanisms, design, chemical modifications, and delivery of ASOs. The administration of FDA-approved ASOs in neurological disorders is described, and current evidence on the safety and efficacy of ASOs in other neurological conditions, including pediatric neurological disorders, is reviewed.
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