Towards the development of a DNA automaton: modular RNA-cleaving deoxyribozyme logic gates regulated by miRNAs.

Advancements in DNA computation have unlocked molecular-scale information processing possibilities, utilizing the intrinsic properties of DNA for complex logical operations with transformative applications in biomedicine. DNA computation shows promise in molecular diagnostics, enabling precise and sensitive detection of genetic mutations and disease biomarkers. Moreover, it holds potential for targeted gene regulation, facilitating personalized therapeutic interventions with enhanced efficacy and reduced side effects. Herein, we have developed six DNAzyme-based logic gates able to process YES, AND, and NOT Boolean logic. The novelty of this work lies in their additional functionalization with a common DNA scaffold for increased cooperativity in input recognition. Moreover, we explored hierarchical input binding to multi-input logic gates, which helped gate optimization. Additionally, we developed a new design of an allosteric hairpin switch used to implement NOT logic. All DNA logic gates achieved the desired true-to-false output signal when detecting a panel of miRNAs, known for their important role in malignancy regulation. This is the first example of DNAzyme-based logic gates having all input-recognizing elements integrated in a single DNA nanostructure, which provides new opportunities for building DNA automatons for diagnosis and therapy of human diseases.

Synthesis and Characterization of [(OH)TeNb5O18](6-) in Water Solution, Comparison with [Nb6O19](8-).

Reaction of [Nb6O19](8-) with H6TeO6 in water gives telluropentaniobate [(OH)TeNb5O18](6-) (1) as single product, which was isolated as Na(+) and mixed Na(+)/K(+) salts. Crystal structures were determined for Na6[(OH)TeNb5O18]·15H2O (Na6-1) and K6Na[Nb(5.5){Te(OH)}(0.5)O(18.5)]·26H2O (K6Na-1). Formation of 1 was monitored with electrospray ionization mass spectrometry (ESI-MS) and (125)Te NMR techniques. Capillary electrophoresis was used to calculate electrophoretic mobilities and radii of the anionic species in solutions of [(OH)TeNb5O18](6-) and [Nb6O19](8-) in borate buffer. No condensation or degradation products were detected. Reactions of 1 with {Cp*Rh}(2+) sources gives 1:1 and 2:1 hybrid polyoxometalate, which are present in solution as a mixture of isomers, as detected by (125)Te NMR. The isomerism is related to various possibilities of coordination of {Cp*Rh}(2+) to different {M3O3} faces, relative to the unique Te atom. According to ESI-MS experiments in water and methanol, rapid redistribution of the organometallic fragments between the 1:1 and 2:1 complexes takes place. The 1:1 complexes are more stable in water, while 2:1 complexes dominate in methanol. X-ray structural analysis of the crystals isolated from 2:1 reaction mixture allowed identification of Na3[{Cp*Rh}2TeNb5O19]·24H2O (Cp*2Rh2-1) with two {Cp*Rh}(2+) fragments capping the opposing faces of the Lindqvist anion.