Title

TALE.Sense: A Versatile DNA Sensor Platform for Live Mammalian Cells.

Document Type

Article

Publication Date

12-21-2021

Publication Title

ACS Synth Biol

Keywords

JGM

JAX Source

ACS Synth Biol 2021 Dec 21 [Online ahead of print]

ISSN

2161-5063

PMID

34931802

DOI

https://doi.org/10.1021/acssynbio.1c00212

Abstract

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.

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