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ACS Synthetic Biology

ACS Synthetic Biology

IF: 3.7
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Optimization of Exon-Skipping Riboswitches and Their Applications to Control Mammalian Cell Fate

Published:18 October 2024 DOI: 10.1021/acssynbio.4c00295 PMID: 39318128
Yoko Nomura,?Narae Kim,?Bochen Zhu,?Muhammad Hamzah,?Haifeng Zhang,?Yohei Yokobayashi

Abstract

Mammalian riboswitches that can regulate transgene expression via RNA-small molecule interaction have promising applications in medicine and biotechnology, as they involve no protein factors that can induce immunogenic reactions and are not dependent on specially engineered promoters. However, the lack of cell-permeable and low-toxicity small molecules and cognate aptamers that can be exploited as riboswitches and the modest switching performance of mammalian riboswitches have limited their applications. In this study, we systematically optimized the design of a riboswitch that regulates exon skipping via an RNA aptamer that binds ASP2905. We examined two design strategies to modulate the stability of the aptamer base stem that blocks the 5' splice site to fine-tune the riboswitch characteristics. Furthermore, an optimized riboswitch was used to generate a mouse embryonic stem cell line that can be chemically induced to differentiate into myogenic cells by activating Myod1 expression and a human embryonic kidney cell line that can be induced to trigger apoptosis by activating BAX expression. The results demonstrate the tight chemical regulation of transgenes in mammalian cells to control their phenotype without exogenous protein factors.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ASP-2905) 792184-90-8 C20H17FN8 46 suppliers Inquiry
ASP-2905) 792184-90-8 C20H17FN8 46 suppliers Inquiry
ASP-2905) 792184-90-8 C20H17FN8 46 suppliers Inquiry
ASP-2905) 792184-90-8 C20H17FN8 46 suppliers Inquiry

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