Harnessing Catalytic RNA Circuits for Construction of Artificial Signaling Pathways in Mammalian Cells.
Chao-Qun WuRuo-Yue WuQiu-Long ZhangLiang-Liang WangYang WangChu DaiChen-Xi ZhangLiang XuPublished in: Angewandte Chemie (International ed. in English) (2024)
Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR-Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA-based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis-related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.
Keyphrases
- genome wide
- poor prognosis
- crispr cas
- nucleic acid
- bioinformatics analysis
- oxidative stress
- genome wide identification
- single cell
- binding protein
- copy number
- gene expression
- genome editing
- genome wide analysis
- artificial intelligence
- machine learning
- mesenchymal stem cells
- pi k akt
- big data
- high throughput
- cell cycle arrest
- crystal structure