Journal article
Small-molecule-based regulation of RNA-delivered circuits in mammalian cells
Nature chemical biology, Vol.14(11), pp.1043-1050
11/01/2018
DOI: 10.1038/s41589-018-0146-9
PMID: 30327560
Abstract
Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (modRNA) and self-replicating RNA (replicon) delivered to mammalian cells. Specifically, we engineer small-molecule-responsive RNA binding proteins to control expression of proteins from RNA-encoded genetic circuits. Coupled with specific modRNA dosages or engineered elements from a replicon, including a subgenomic promoter library, we demonstrate the capability to externally regulate the timing and level of protein expression. These control mechanisms facilitate the construction of ON, OFF, and two-output switches, with potential therapeutic applications such as inducible cancer immunotherapies. These circuits, along with other synthetic networks that can be developed using these tools, will expand the utility of synthetic mRNA as a therapeutic modality.
Details
- Title: Subtitle
- Small-molecule-based regulation of RNA-delivered circuits in mammalian cells
- Creators
- Tyler E Wagner - Boston UniversityJacob R Becraft - Massachusetts Institute of TechnologyKatie Bodner - Massachusetts Institute of TechnologyBrian Teague - Massachusetts Institute of TechnologyXin Zhang - Massachusetts Institute of TechnologyAmanda Woo - Massachusetts Institute of TechnologyEly Porter - Massachusetts Institute of TechnologyBremy Alburquerque - Massachusetts Institute of TechnologyBrian Dobosh - Massachusetts Institute of TechnologyOliwia Andries - Ghent UniversityNiek N Sanders - Ghent UniversityJacob Beal - RTXDouglas Densmore - Boston UniversityTasuku Kitada - Massachusetts Institute of TechnologyRon Weiss - Massachusetts Institute of Technology
- Resource Type
- Journal article
- Publication Details
- Nature chemical biology, Vol.14(11), pp.1043-1050
- DOI
- 10.1038/s41589-018-0146-9
- PMID
- 30327560
- ISSN
- 1552-4450
- eISSN
- 1552-4469
- Language
- English
- Date published
- 11/01/2018
- Academic Unit
- Electrical and Computer Engineering
- Record Identifier
- 9984627228102771
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