Directing cellular information flow via CRISPR signal conductors.
The complex phenotypes of eukaryotic cells are controlled by decision-making circuits and signaling pathways. A key obstacle to implementing artificial connections in signaling networks has been the lack of synthetic devices for efficient sensing, processing and control of biological signals. By extending sgRNAs to include modified riboswitches that recognize specific signals, we can create CRISPR-Cas9-based 'signal conductors' that regulate transcription of endogenous genes in response to external or internal signals of interest. These devices can be used to construct all the basic types of Boolean logic gates that perform logical signal operations in mammalian cells without needing the layering of multiple genetic circuits. They can also be used to rewire cellular signaling events by constructing synthetic links that couple different signaling pathways. Moreover, this approach can be applied to redirect oncogenic signal transduction by controlling simultaneous bidirectional (ON-OFF) gene transcriptions, thus enabling reprogramming of the fate of cancer cells.
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Yuchen
Y
Liu
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Yonghao
Y
Zhan
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Zhicong
Z
Chen
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Anbang
A
He
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.|State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Jianfa
J
Li
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Hanwei
H
Wu
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Li
L
Liu
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Chengle
C
Zhuang
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Junhao
J
Lin
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Xiaoqiang
X
Guo
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Qiaoxia
Q
Zhang
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Weiren
W
Huang
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Zhiming
Z
Cai
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D064113:CRISPR-Cas Systems / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics; D010957:Plasmids; D000094704:RNA, Guide, CRISPR-Cas Systems / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D020349:Surface Plasmon Resonance; D015533:Transcriptional Activation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D000094704:RNA, Guide, CRISPR-Cas Systems; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A