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RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays

Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USA
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Author to whom correspondence should be addressed.
Academic Editors: Maria Chatzopoulou, Angela Russell and Simona Rapposelli
Molecules 2021, 26(8), 2263; https://doi.org/10.3390/molecules26082263
Received: 26 February 2021 / Revised: 5 April 2021 / Accepted: 9 April 2021 / Published: 14 April 2021
(This article belongs to the Special Issue Phenotypic Screening)
RNA splicing is an essential step in producing mature messenger RNA (mRNA) and other RNA species. Harnessing RNA splicing modifiers as a new pharmacological modality is promising for the treatment of diseases caused by aberrant splicing. This drug modality can be used for infectious diseases by disrupting the splicing of essential pathogenic genes. Several antisense oligonucleotide splicing modifiers were approved by the U.S. Food and Drug Administration (FDA) for the treatment of spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). Recently, a small-molecule splicing modifier, risdiplam, was also approved for the treatment of SMA, highlighting small molecules as important warheads in the arsenal for regulating RNA splicing. The cellular targets of these approved drugs are all mRNA precursors (pre-mRNAs) in human cells. The development of novel RNA-targeting splicing modifiers can not only expand the scope of drug targets to include many previously considered “undruggable” genes but also enrich the chemical-genetic toolbox for basic biomedical research. In this review, we summarized known splicing modifiers, screening methods for novel splicing modifiers, and the chemical space occupied by the small-molecule splicing modifiers. View Full-Text
Keywords: alternative splicing; high-throughput screening; antisense oligonucleotide; small molecule; splicing modifier; RNA-targeting alternative splicing; high-throughput screening; antisense oligonucleotide; small molecule; splicing modifier; RNA-targeting
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MDPI and ACS Style

Tang, Z.; Zhao, J.; Pearson, Z.J.; Boskovic, Z.V.; Wang, J. RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays. Molecules 2021, 26, 2263. https://doi.org/10.3390/molecules26082263

AMA Style

Tang Z, Zhao J, Pearson ZJ, Boskovic ZV, Wang J. RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays. Molecules. 2021; 26(8):2263. https://doi.org/10.3390/molecules26082263

Chicago/Turabian Style

Tang, Zhichao; Zhao, Junxing; Pearson, Zach J.; Boskovic, Zarko V.; Wang, Jingxin. 2021. "RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays" Molecules 26, no. 8: 2263. https://doi.org/10.3390/molecules26082263

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