Programmable RNA sensing for cell monitoring and manipulation

Yongjun Qian, Jiayun Li, Shengli Zhao, Elizabeth A. Matthews, Michael Adoff, Weixin Zhong, Xu An, Michele Yeo, Christine Park, Xiaolu Yang, Bor-Shuen Wang, Derek G. Southwell and Z. Josh Huang ()
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Yongjun Qian: Duke University Medical Center
Jiayun Li: Cold Spring Harbor
Shengli Zhao: Duke University Medical Center
Elizabeth A. Matthews: Duke University Medical Center
Michael Adoff: Duke University Medical Center
Weixin Zhong: Duke University Medical Center
Xu An: Duke University Medical Center
Michele Yeo: Duke University Medical Center
Christine Park: Duke University Medical Center
Xiaolu Yang: Duke University Medical Center
Bor-Shuen Wang: Cold Spring Harbor
Derek G. Southwell: Duke University Medical Center
Z. Josh Huang: Duke University Medical Center

Nature, 2022, vol. 610, issue 7933, 713-721

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-05280-1

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