ABSTRACT
Synthetic mRNA circuits commonly sense input to produce binary output signals for cell separation. Based on virus-origin cap-independent translation initiation machinery and RBP-aptamer interaction, we designed smart synthetic mRNA-based circuits that sense single input molecules to bidirectionally tune output signals in an orthogonal manner, enabling high-resolution separation of cell populations.
Subject(s)
Cell Separation , RNA, Messenger , Humans , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/metabolism , Cell Separation/methods , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Color-tunable organic light-emitting diodes (CT-OLEDs) have a large color-tuning range, high efficiency and operational stability at practical luminance, making them ideal for human-machine interactive terminals of wearable biomedical devices. However, the device operational lifetime of CT-OLEDs is currently far from reaching practical requirements. To address this problem, a tetradentate Pt(II) complex named tetra-Pt-dbf, which can emit efficiently in both monomer and aggregation states, is designed. This emitter has high Td of 508 °C and large intermolecular bonding energy of -52.0 kcal molâ»1, which improve its thermal/chemical stability. This unique single-emitter CT-OLED essentially avoids the "color-aging issue" and achieves a large color-tuning span (red to yellowish green) and a high external quantum efficiency ï¼EQEï¼ of ≈30% at 1000 cd m-2 as well as an EQE of above 25% at 10000 cd m-2. A superior LT90 operational lifetime of 520,536 h at a functional luminance of 100 cd m-2, which is over 20 times longer than the state-of-the-art CT-OLEDs, is estimated. To demonstrate the potential application of such OLEDs in wearable biomedical devices, a simple electromyography (EMG)-visualization system is fabricated using the CT-OLEDs.
ABSTRACT
Synthetic mRNA switches are powerful cell fate manipulation tools that sense cellular input molecules to directly control protein expression at the translational level. The lack of available switch designs that can mimic the natural sophisticated protein regulation is a fundamental issue that limits the application of synthetic mRNA switches. Here we report a new set of synthetic mRNA switches by incorporating self-feedback loop machineries to dynamically control protein expression levels upon sensing cellular microRNAs. We redesigned the coding region of the switch to express output protein along with mRNA regulatory proteins. RNA-binding proteins (RBPs) and RBP-binding RNA motifs (aptamers) guide the regulatory proteins to act on their own mRNAs, enhancing or flattening the effect of microRNA sensing. Importantly, we demonstrated that the switches with the positive feedback feature can enlarge a high-or-low microRNA effect into a nearly all-or-none pattern, substantially boosting the use of synthetic mRNA switches as high-performance microRNA sensors or binary cell regulation tools. We believe these novel mRNA switch designs provide new strategies to construct complex mRNA-based genetic circuits for future molecular sensing and cell engineering.