Programmable RNA sensing for cell monitoring and manipulation

Qian, Yongjun, Li, Jiayun, Zhao, Shengli, Matthews, Elizabeth A, Adoff, Michael, Zhong, Weixin, An, Xu, Yeo, Michele, Park, Christine, Yang, Xiaolu, Wang, Bor-Shuen, Southwell, Derek G, Huang, Z Josh (October 2022) Programmable RNA sensing for cell monitoring and manipulation. Nature. ISSN 0028-0836

URL: https://www.ncbi.nlm.nih.gov/pubmed/36198803
DOI: 10.1038/s41586-022-05280-1

Abstract

RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.

Item Type: Paper
CSHL Authors:
Communities: CSHL labs > Fearon lab
CSHL labs > Huang lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 5 October 2022
Date Deposited: 10 Oct 2022 13:45
Last Modified: 10 Oct 2022 13:45
URI: https://repository.cshl.edu/id/eprint/40733

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