posted on 2021-12-21, 17:05authored byAziz Taghbalout, Nathaniel Jillette, Albert W. Cheng
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.