| RRC ID |
81777
|
| 著者 |
Nomura Y, Kim N, Zhu B, Hamzah M, Zhang H, Yokobayashi Y.
|
| タイトル |
Optimization of Exon-Skipping Riboswitches and Their Applications to Control Mammalian Cell Fate.
|
| ジャーナル |
ACS Synth Biol
|
| 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.
|
| 公開日 |
2024-9-24
|
| DOI |
10.1021/acssynbio.4c00295
|
| PMID |
39318128
|
| PMC |
PMC11494654
|
| MeSH |
Animals
Apoptosis / drug effects
Apoptosis / genetics
Aptamers, Nucleotide* / metabolism
Cell Differentiation
Cell Line
Exons* / genetics
HEK293 Cells
Humans
Mice
Mouse Embryonic Stem Cells / metabolism
MyoD Protein* / genetics
MyoD Protein* / metabolism
Riboswitch* / genetics
Transgenes
bcl-2-Associated X Protein / genetics
bcl-2-Associated X Protein / metabolism
|
| IF |
4.411
|
| リソース情報 |
| ヒト・動物細胞 |
BRC6(AES0010) |
| 遺伝子材料 |
pCAGGS-LIF (RDB09182) |
