scholarly journals Fluorogenic RNA Aptamers: A Nano-platform for Fabrication of Simple and Combinatorial Logic Gates

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 984 ◽  
Author(s):  
Victoria Goldsworthy ◽  
Geneva LaForce ◽  
Seth Abels ◽  
Emil Khisamutdinov

RNA aptamers that bind non-fluorescent dyes and activate their fluorescence are highly sensitive, nonperturbing, and convenient probes in the field of synthetic biology. These RNA molecules, referred to as light-up aptamers, operate as molecular nanoswitches that alter folding and fluorescence function in response to ligand binding, which is important in biosensing and molecular computing. Herein, we demonstrate a conceptually new generation of smart RNA nano-devices based on malachite green (MG)-binding RNA aptamer, which fluorescence output controlled by addition of short DNA oligonucleotides inputs. Four types of RNA switches possessing AND, OR, NAND, and NOR Boolean logic functions were created in modular form, allowing MG dye binding affinity to be changed by altering 3D conformation of the RNA aptamer. It is essential to develop higher-level logic circuits for the production of multi-task nanodevices for data processing, typically requiring combinatorial logic gates. Therefore, we further designed and synthetized higher-level half adder logic circuit by “in parallel” integration of two logic gates XOR and AND within a single RNA nanoparticle. The design utilizes fluorescence emissions from two different RNA aptamers: MG-binding RNA aptamer (AND gate) and Broccoli RNA aptamer that binds DFHBI dye (XOR gate). All computationally designed RNA devices were synthesized and experimentally tested in vitro. The ability to design smart nanodevices based on RNA binding aptamers offers a new route to engineer “label-free” ligand-sensing regulatory circuits, nucleic acid detection systems, and gene control elements.

2019 ◽  
Vol 116 (15) ◽  
pp. 7214-7219 ◽  
Author(s):  
Hyojin Kim ◽  
Daniel Bojar ◽  
Martin Fussenegger

Controlling gene expression with sophisticated logic gates has been and remains one of the central aims of synthetic biology. However, conventional implementations of biocomputers use central processing units (CPUs) assembled from multiple protein-based gene switches, limiting the programming flexibility and complexity that can be achieved within single cells. Here, we introduce a CRISPR/Cas9-based core processor that enables different sets of user-defined guide RNA inputs to program a single transcriptional regulator (dCas9-KRAB) to perform a wide range of bitwise computations, from simple Boolean logic gates to arithmetic operations such as the half adder. Furthermore, we built a dual-core CPU combining two orthogonal core processors in a single cell. In principle, human cells integrating multiple orthogonal CRISPR/Cas9-based core processors could offer enormous computational capacity.


Author(s):  
Lakshmi kiran Mukkara ◽  
K.Venkata Ramanaiah

<p>Any digital circuit is made with fundamental building blocks i.e. logic gates. Artificial neural networks (ANN) became an emerging area in various applications such as prediction problems, pattern recognition, and robotics &amp; system identification due to its processing capabilities with parallel architecture. Realization of Boolean logic with neural networks is referred as neuronal logic. ANN computes faster as it requires of low and simple precision computations. Also, it requires economic and low precision hardware. Neural network contains more number of addition and multiplication processes. It is known that CSD algorithm computes faster than conventional or standard multipliers. In this paper, VLSI implementation of neuronal half adder with CSD algorithm is proposed and implemented in FPGA. The results are compared with that of conventional and vedic multiplier. It is observed that CSD algorithm provides lowest delay and low power consumption in comparison with vedic algorithm and conventional method but at the expense of minimum area.</p>


2019 ◽  
Vol 55 (68) ◽  
pp. 10096-10099 ◽  
Author(s):  
Lele Sheng ◽  
Yunhao Lu ◽  
Sha Deng ◽  
Xinyu Liao ◽  
Kaixiang Zhang ◽  
...  

We report a light-up RNA aptamer-based transcription aptasensor, enabling sensitive, label-free and culture-free detection of intact foodborne pathogens.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charles El Helou ◽  
Philip R. Buskohl ◽  
Christopher E. Tabor ◽  
Ryan L. Harne

AbstractIntegrated circuits utilize networked logic gates to compute Boolean logic operations that are the foundation of modern computation and electronics. With the emergence of flexible electronic materials and devices, an opportunity exists to formulate digital logic from compliant, conductive materials. Here, we introduce a general method of leveraging cellular, mechanical metamaterials composed of conductive polymers to realize all digital logic gates and gate assemblies. We establish a method for applying conductive polymer networks to metamaterial constituents and correlate mechanical buckling modes with network connectivity. With this foundation, each of the conventional logic gates is realized in an equivalent mechanical metamaterial, leading to soft, conductive matter that thinks about applied mechanical stress. These findings may advance the growing fields of soft robotics and smart mechanical matter, and may be leveraged across length scales and physics.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3178 ◽  
Author(s):  
Morgan Chandler ◽  
Tatiana Lyalina ◽  
Justin Halman ◽  
Lauren Rackley ◽  
Lauren Lee ◽  
...  

RNA aptamers selected to bind fluorophores and activate their fluorescence offer a simple and modular way to visualize native RNAs in cells. Split aptamers which are inactive until the halves are brought within close proximity can become useful for visualizing the dynamic actions of RNA assemblies and their interactions in real time with low background noise and eliminated necessity for covalently attached dyes. Here, we design and test several sets of F30 Broccoli aptamer splits, that we call fluorets, to compare their relative fluorescence and physicochemical stabilities. We show that the splits can be simply assembled either through one-pot thermal annealing or co-transcriptionally, thus allowing for direct tracking of transcription reactions via the fluorescent response. We suggest a set of rules that enable for the construction of responsive biomaterials that readily change their fluorescent behavior when various stimuli such as the presence of divalent ions, exposure to various nucleases, or changes in temperature are applied. We also show that the strand displacement approach can be used to program the controllable fluorescent responses in isothermal conditions. Overall, this work lays a foundation for the future development of dynamic systems for molecular computing which can be used to monitor real-time processes in cells and construct biocompatible logic gates.


2010 ◽  
Vol 12 (32) ◽  
pp. 9176 ◽  
Author(s):  
Anjum Qureshi ◽  
Yasar Gurbuz ◽  
Saravan Kallempudi ◽  
Javed H. Niazi

2017 ◽  
Vol 89 (18) ◽  
pp. 9734-9741 ◽  
Author(s):  
Jiao Yang Lu ◽  
Xin Xing Zhang ◽  
Wei Tao Huang ◽  
Qiu Yan Zhu ◽  
Xue Zhi Ding ◽  
...  

2006 ◽  
Vol 1 (2) ◽  
pp. 637-640 ◽  
Author(s):  
Nikolai Windbichler ◽  
Renée Schroeder

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4785
Author(s):  
Enrico Kittel-Boselli ◽  
Karla Elizabeth González Soto ◽  
Liliana Rodrigues Loureiro ◽  
Anja Hoffmann ◽  
Ralf Bergmann ◽  
...  

Clinical translation of novel immunotherapeutic strategies such as chimeric antigen receptor (CAR) T-cells in acute myeloid leukemia (AML) is still at an early stage. Major challenges include immune escape and disease relapse demanding for further improvements in CAR design. To overcome such hurdles, we have invented the switchable, flexible and programmable adaptor Reverse (Rev) CAR platform. This consists of T-cells engineered with RevCARs that are primarily inactive as they express an extracellular short peptide epitope incapable of recognizing surface antigens. RevCAR T-cells can be redirected to tumor antigens and controlled by bispecific antibodies cross-linking RevCAR T- and tumor cells resulting in tumor lysis. Remarkably, the RevCAR platform enables combinatorial tumor targeting following Boolean logic gates. We herein show for the first time the applicability of the RevCAR platform to target myeloid malignancies like AML. Applying in vitro and in vivo models, we have proven that AML cell lines as well as patient-derived AML blasts were efficiently killed by redirected RevCAR T-cells targeting CD33 and CD123 in a flexible manner. Furthermore, by targeting both antigens, a Boolean AND gate logic targeting could be achieved using the RevCAR platform. These accomplishments pave the way towards an improved and personalized immunotherapy for AML patients.


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