Readthrough compounds for nonsense mutations: bridging the translational gap

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作   者：

Spelier, Sacha;  van Doorn, Eveline P. M.;  van der Ent, Cornelis K.;  Beekman, Jeffrey M.;  Koppens, Martijn A. J.; 

作者机构：

Univ Utrecht; 

关键词：

MESSENGER-RNA;  PTC124 TREATMENT;  DOUBLE-BLIND;  DUCHENNE MUSCULAR-DYSTROPHY;  READ-THROUGH;  CYSTIC-FIBROSIS;  EXON JUNCTION COMPLEX;  SUPPRESSION;  STOP CODON RECOGNITION;  ATALUREN; 

期刊名称：

Trends in molecular medicine.

i s s n：

1471-4914

年卷期：

2023 年 29 卷 4 期

页   码：

297-314

页   码：

摘   要：

Approximately 10% of all pathological mutations are nonsense mutations that are responsible for several severe genetic diseases for which no treatment regimens are currently available. The most widespread strategy for treating nonsense muta-tions is by enhancing ribosomal readthrough of premature termination codons (PTCs) to restore the production of the full-length protein. In the past decade sev-eral compounds with readthrough potential have been identified. However, although preclinical results on these compounds are promising, clinical studies have not yielded positive outcomes. We review preclinical and clinical research related to readthrough compounds and characterize factors that contribute to the observed translational gap.