TALE.Sense: A Versatile DNA Sensor Platform for Live Mammalian Cells.
Aziz TaghbaloutNathaniel JilletteAlbert Wu ChengPublished in: ACS synthetic biology (2021)
Here we describe TALE.Sense, a versatile platform for sensing DNA sequences in live mammalian cells enabling programmable generation of a customable response that discerns cells containing specified sequence targets. The platform is based on the programmable DNA binding of transcription activator-like effector (TALE) coupled to conditional intein-reconstitution producing a trans-spliced ON-switch for a response circuit. TALE.Sense shows higher efficiency and dynamic range when compared to the reported zinc-finger based DNA-sensor in detecting same DNA sequences. Swapping transcriptional activation modules and introducing SunTag-based amplification loops to TALE.Sense circuits augment detection efficiency of the DNA sensor. The TALE.Sense platform shows versatility when applied to a range of target sites, indicating its suitability for applications to identify live cell variants with anticipated DNA sequences. TALE.Sense could be integrated with other cellular or synthetic circuits by using specified DNA sequences as control-switches, thus expanding the scope in connecting inducible modules for synthetic biology.
Keyphrases
- circulating tumor
- cell free
- single molecule
- nucleic acid
- dna binding
- high throughput
- transcription factor
- gene expression
- circulating tumor cells
- induced apoptosis
- dendritic cells
- signaling pathway
- dna methylation
- immune response
- cell cycle arrest
- inflammatory response
- copy number
- sensitive detection
- real time pcr
- loop mediated isothermal amplification
- type iii
- pi k akt