RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays
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 disr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/8/2263 |
| _version_ | 1797537802828644352 |
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| author | Zhichao Tang Junxing Zhao Zach J. Pearson Zarko V. Boskovic Jingxin Wang |
| author_facet | Zhichao Tang Junxing Zhao Zach J. Pearson Zarko V. Boskovic Jingxin Wang |
| author_sort | Zhichao Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:21:26Z |
| format | Article |
| id | doaj.art-a7d2255430ac4a0c9683e76b0a7cb251 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:21:26Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a7d2255430ac4a0c9683e76b0a7cb2512023-11-21T15:30:00ZengMDPI AGMolecules1420-30492021-04-01268226310.3390/molecules26082263RNA-Targeting Splicing Modifiers: Drug Development and Screening AssaysZhichao Tang0Junxing Zhao1Zach J. Pearson2Zarko V. Boskovic3Jingxin Wang4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USADepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USADepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USADepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USADepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, USARNA 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.https://www.mdpi.com/1420-3049/26/8/2263alternative splicinghigh-throughput screeningantisense oligonucleotidesmall moleculesplicing modifierRNA-targeting |
| spellingShingle | Zhichao Tang Junxing Zhao Zach J. Pearson Zarko V. Boskovic Jingxin Wang RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays Molecules alternative splicing high-throughput screening antisense oligonucleotide small molecule splicing modifier RNA-targeting |
| title | RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays |
| title_full | RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays |
| title_fullStr | RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays |
| title_full_unstemmed | RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays |
| title_short | RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays |
| title_sort | rna targeting splicing modifiers drug development and screening assays |
| topic | alternative splicing high-throughput screening antisense oligonucleotide small molecule splicing modifier RNA-targeting |
| url | https://www.mdpi.com/1420-3049/26/8/2263 |
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