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Development of a new caged intein for multi-input conditional translation of synthetic mRNA.
- Source :
-
Scientific Reports . 5/1/2024, Vol. 14 Issue 1, p1-10. 10p. - Publication Year :
- 2024
-
Abstract
- mRNA medicines can be used to express therapeutic proteins, but the production of such proteins in non-target cells has a risk of adverse effects. To accurately distinguish between therapeutic target and nontarget cells, it is desirable to utilize multiple proteins expressed in each cell as indicators. To achieve such multi-input translational regulation of mRNA medicines, in this study, we engineered Rhodothermus marinus (Rma) DnaB intein to develop "caged Rma DnaB intein" that enables conditional reconstitution of full-length translational regulator protein from split fragments. By combining the caged Rma DnaB intein, the split translational regulator protein, and target protein-binding domains, we succeeded in target protein-dependent translational repression of mRNA in human cells. In addition, the caged Rma intein showed orthogonality to the previously reported Nostoc punctiforme (Npu) DnaE-based caged intein. Finally, by combining these two orthogonal caged inteins, we developed an mRNA-based logic gate that regulates translation based on the expression of multiple intracellular proteins. This study provides important information to develop safer mRNA medicines. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RNA regulation
*THERAPEUTIC use of proteins
*LOGIC circuits
*MESSENGER RNA
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 14
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 177000504
- Full Text :
- https://doi.org/10.1038/s41598-024-60809-w