Engineering Synthetic CopT/A-Based Genetic Biosensors for miRNA Imaging and Functional Gene Regulation.
Chuanxian ZhangXiaorui ShiChu TangYarong DuWenjie ShuFu WangPublished in: Analytical chemistry (2023)
Synthetic genetic biosensors that can operate at the transcriptional and translation levels have been widely applied in the control of cellular behaviors and functions. However, the regulation of genetic circuits is often accompanied by the introduction of exogenous substances or the endogenous generation of inhibitory products, which would bring uncontrollable hazards to biological safety and reduce the efficiency of the system. Here, we described a miRNA-responsive CopT-CopA (miCop) genetic biosensor system to realize real-time monitoring of the intracellular expression of miRNA-124a during neurogenesis or miRNA-122 under the stimulation of extracellular drugs in living cells and animals. Furthermore, to prove the modularity of the system, we engineered this miCop to tune the expression of the DTA (diphtheria toxin A) gene and showed its powerful capacity to kill cancer cells by inducing apoptosis and cell cycle arrest based on miRNA response. This study provides an effective means to couple miRNA sensing with miRNA-responsive gene modulation, which may open up new diagnostic or therapeutic applications.
Keyphrases
- genome wide
- cell cycle arrest
- copy number
- living cells
- poor prognosis
- cell death
- escherichia coli
- high resolution
- dna methylation
- gene expression
- cell proliferation
- binding protein
- endoplasmic reticulum stress
- transcription factor
- quantum dots
- long non coding rna
- blood brain barrier
- subarachnoid hemorrhage
- signaling pathway
- heat shock protein
- label free
- reactive oxygen species
- brain injury