Back to Search
Start Over
Genetically Encoded Protein Thermometer Enables Precise Electrothermal Control of Transgene Expression
- Source :
- Advanced Science, 8 (21), Advanced Science, Advanced Science, Vol 8, Iss 21, Pp n/a-n/a (2021)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Body temperature is maintained at around 37 degrees C in humans, but may rise to 40 degrees C or more during high-grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat-shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37-40 degrees C by linking a mutant coiled-coil temperature-responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT-transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature- and exposure-time-dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT-controlled insulin production cassette in a mouse model of type-1 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell-based therapy, and may also have potential for next-generation treatment of fever-associated medical conditions.<br />Advanced Science, 8 (21)<br />ISSN:2198-3844
- Subjects :
- Thermometers
Science
General Chemical Engineering
Transgene
Cell
Mutant
General Physics and Astronomy
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cell Line
Diabetes Mellitus, Experimental
Mice
03 medical and health sciences
0302 clinical medicine
In vivo
medicine
Animals
Humans
Insulin
General Materials Science
Promoter Regions, Genetic
Transcription factor
Research Articles
030304 developmental biology
Regulation of gene expression
0303 health sciences
Reporter gene
diabetes
Chemistry
gene switches
Temperature
General Engineering
Promoter
Alkaline Phosphatase
Cell biology
gene regulation
synthetic biology
temperature
medicine.anatomical_structure
030217 neurology & neurosurgery
Research Article
Plasmids
Subjects
Details
- ISSN :
- 21983844
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Advanced Science
- Accession number :
- edsair.doi.dedup.....92c49501bdcda78537a1b31da7fb857f