Scalable biological signal recording in mammalian cells using Cas12a base editors.

ABSTRACT: Biological signal recording enables the study of molecular inputs experienced throughout cellular history. However, current methods are limited in their ability to scale up beyond a single signal in mammalian contexts. Here, we develop an approach using a hyper-efficient dCas12a base editor for multi-signal parallel recording in human cells. We link signals of interest to expression of guide RNAs to catalyze specific nucleotide conversions as a permanent record, enabled by Cas12's guide-processing abilities. We show this approach is plug-and-play with diverse biologically relevant inputs and extend it for more sophisticated applications, including recording of time-delimited events and history of chimeric antigen receptor T cells' antigen exposure. We also demonstrate efficient recording o

SUBMITTER: Kempton HR 

PROVIDER: S-EPMC9246900 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature