Article ; Online: Engineering U1-Based Tetracycline-Inducible Riboswitches to Control Gene Expression in Mammals.
ACS nano
2023 Volume 17, Issue 23, Page(s) 23331–23346
Abstract: Synthetic riboswitches are promising regulatory devices due to their small size, lack of immunogenicity, and ability to fine-tune gene expression in the absence of exogenous trans-acting factors. Based on a gene inhibitory system developed at our lab, ... ...
| Abstract | Synthetic riboswitches are promising regulatory devices due to their small size, lack of immunogenicity, and ability to fine-tune gene expression in the absence of exogenous trans-acting factors. Based on a gene inhibitory system developed at our lab, termed U1snRNP interference (U1i), we developed tetracycline (TC)-inducible riboswitches that modulate mRNA polyadenylation through selective U1 snRNP recruitment. First, we engineered different TC-U1i riboswitches, which repress gene expression unless TC is added, leading to inductions of gene expression of 3-to-4-fold. Second, we developed a technique called Systematic Evolution of Riboswitches by Exponential Enrichment (SEREX), to isolate riboswitches with enhanced U1 snRNP binding capacity and activity, achieving inducibilities of up to 8-fold. Interestingly, by multiplexing riboswitches we increased inductions up to 37-fold. Finally, we demonstrated that U1i-based riboswitches are dose-dependent and reversible and can regulate the expression of reporter and endogenous genes in culture cells and mouse models, resulting in attractive systems for gene therapy applications. Our work probes SEREX as a much-needed technology for the |
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| MeSH term(s) | Animals ; Mice ; Riboswitch/genetics ; Ribonucleoprotein, U1 Small Nuclear/genetics ; Tetracycline/pharmacology ; Anti-Bacterial Agents ; Mammals/genetics ; Gene Expression |
| Chemical Substances | Riboswitch ; Ribonucleoprotein, U1 Small Nuclear ; Tetracycline (F8VB5M810T) ; Anti-Bacterial Agents |
| Language | English |
| Publishing date | 2023-11-16 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 1936-086X |
| ISSN (online) | 1936-086X |
| DOI | 10.1021/acsnano.3c01994 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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