Scalable recombinase-based gene expression cascades
Name
s41467-021-22978-4.pdf
Description
Published version
Size
3.05 MB
Format
Adobe PDF
Checksum (MD5)
64b299741b06316f056256500ce5a300
Author(s)
Kim, Tackhoon
Weinberg, Benjamin
Wong, Wilson
Lu, Timothy K
Date Issued
2021
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Kim, Tackhoon, Weinberg, Benjamin, Wong, Wilson and Lu, Timothy K. 2021. "Scalable recombinase-based gene expression cascades." Nature Communications, 12 (1).
Version
Final published version
Abstract
AbstractTemporal modulation of the expression of multiple genes underlies complex complex biological phenomena. However, there are few scalable and generalizable gene circuit architectures for the programming of sequential genetic perturbations. Here, we describe a modular recombinase-based gene circuit architecture, comprising tandem gene perturbation cassettes (GPCs), that enables the sequential expression of multiple genes in a defined temporal order by alternating treatment with just two orthogonal ligands. We use tandem GPCs to sequentially express single-guide RNAs to encode transcriptional cascades that trigger the sequential accumulation of mutations. We build an all-in-one gene circuit that sequentially edits genomic loci, synchronizes cells at a specific stage within a gene expression cascade, and deletes itself for safety. Tandem GPCs offer a multi-tiered cellular programming tool for modeling multi-stage genetic changes, such as tumorigenesis and cellular differentiation.
MIT Department
Massachusetts Institute of Technology. Research Laboratory of Electronics
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-021-22978-4
