HCS-Splice: A High-Content Screening Method to Advance the Discovery of RNA Splicing-Modulating Therapeutics.
FTDP-17
MAPT
alternative splicing
drug discovery
exon-skipping
high content screening
nucleic acids therapeutics
siRNA
two-colour (GFP/RFP) fluorescent reporter
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
28 07 2023
28 07 2023
Historique:
received:
25
06
2023
revised:
10
07
2023
accepted:
13
07
2023
medline:
14
8
2023
pubmed:
11
8
2023
entrez:
11
8
2023
Statut:
epublish
Résumé
Nucleic acid therapeutics have demonstrated an impressive acceleration in recent years. They work through multiple mechanisms of action, including the downregulation of gene expression and the modulation of RNA splicing. While several drugs based on the former mechanism have been approved, few target the latter, despite the promise of RNA splicing modulation. To improve our ability to discover novel RNA splicing-modulating therapies, we developed HCS-Splice, a robust cell-based High-Content Screening (HCS) assay. By implementing the use of a two-colour (GFP/RFP) fluorescent splicing reporter plasmid, we developed a versatile, effective, rapid, and robust high-throughput strategy for the identification of potent splicing-modulating molecules. The HCS-Splice strategy can also be used to functionally confirm splicing mutations in human genetic disorders or to screen drug candidates. As a proof-of-concept, we introduced a dementia-related splice-switching mutation in the Microtubule-Associated Protein Tau (
Identifiants
pubmed: 37566038
pii: cells12151959
doi: 10.3390/cells12151959
pmc: PMC10417277
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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