I am a scientist specialized in mitochondria and genetics, but above all, I am just curious guy who loves learning new things.
Forget about 3D printing, here comes DNA origami!
Forget about 3D printing, here comes DNA origami!
In 10 seconds? DNA is the most important piece of our biology, but now it may also become the future of technology, as super efficient hard drives or nano-material to build anything from smiley faces to very tiny robots!
Don’t believe it? Thanks to its extreme durability and density, DNA is starting to be used to store digital data, sort of a super small and durable computer hard drive (Erlich et al, 2017). And because of these same qualities, plus the possibility of manipulating its sequence and structure, DNA has been proposed as the perfect building blocks for future nano technology (Wagenbauer et al, 2017).
And what is all the fuss about nano technology? Nano technology is very, very, small technology, which will allow to work in very, very small places. Kind of like building a very tiny hammer to nail a very tiny painting in a very tiny house. And this could have all sorts of uses, for instance, to create microscopic tubes that will take a medication into a specific kind of cell, avoiding side effects or over dosing. Or to build very small smiley faces! (Han et al, 2017).
And how can DNA do that? Researchers have found a technic that allows to fold DNA into any kind of structure, kind of like doing origami with a piece of paper, but much, much, smaller and resistant. And these structures could be used as specific delivery systems (Hadorn et al, 2012), kind of like Amazon drones for cells, or to build nano machines that could undertake specific tasks within the cell.
These DNA structures can also move? They can even walk! Researchers from Israel managed to build a DNA bipedal walker that walks on a DNA track! (Tomov et al, 2017) And by using chemical microfluids they can command the walker how many steps to make and when to stop, controlling its direction and speed.
So, not only we will be able to “print” any kind of 3D structure on DNA but also give it a motor to create the super small machines of the future.
Targeted drug delivery, such as acetylcholinesterase inhibitors, has been tested to treat Alzeihmer’s Disease, but the delivery of these drugs to the Central Nervous System (CNS) has low efficiency due to the impediments of the blood-brain barrier (BBB). DNA nano carriers could be the solution for efficient nano-drug delivery through the BBB into the CNS (Karthivashan et al, 2018).
Abstract: DNA is an attractive medium to store digital information. Here we report a storage strategy, called DNA Fountain, that is highly robust and approaches the information capacity per nucleotide. Using our approach, we stored a full computer operating system, movie, and other files with a total of 2.14 × 10(6) bytes in DNA oligonucleotides and perfectly retrieved the information from a sequencing coverage equivalent to a single tile of Illumina sequencing. We also tested a process that can allow 2.18 × 10(15) retrievals using the original DNA sample and were able to perfectly decode the data. Finally, we explored the limit of our architecture in terms of bytes per molecule and obtained a perfect retrieval from a density of 215 petabytes per gram of DNA, orders of magnitude higher than previous reports.
Pub.: 04 Mar '17, Pinned: 23 Jan '18
Abstract: In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with the aging population. Alzheimer's disease (AD) is one of the most commonly reported neurodegenerative disorders, and it is estimated to increase by roughly 30% among the aged population. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates - such as acetylcholinesterase inhibitors are currently utilized as an effective clinical therapy. However, targeted drug delivery of these drugs to the central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, and reduced efficiency due to the impediments of the blood-brain barrier (BBB). Current advances in nanotechnology present opportunities to overcome such limitations in delivering active drug candidates. Nanodrug delivery systems are promising in targeting several therapeutic moieties by easing the penetration of drug molecules across the CNS and improving their bioavailability. Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have been adapted to develop successful therapeutics with sustained release and improved efficacy. Here, we discuss few recently updated nano-drug delivery applications that have been adapted in the field of AD therapeutics, and future prospects on potential molecular targets for nano-drug delivery systems.
Pub.: 20 Jan '18, Pinned: 23 Jan '18
Abstract: Natural biomolecular assemblies such as molecular motors, enzymes, viruses and subcellular structures often form by self-limiting hierarchical oligomerization of multiple subunits. Large structures can also assemble efficiently from a few components by combining hierarchical assembly and symmetry, a strategy exemplified by viral capsids. De novo protein design and RNA and DNA nanotechnology aim to mimic these capabilities, but the bottom-up construction of artificial structures with the dimensions and complexity of viruses and other subcellular components remains challenging. Here we show that natural assembly principles can be combined with the methods of DNA origami to produce gigadalton-scale structures with controlled sizes. DNA sequence information is used to encode the shapes of individual DNA origami building blocks, and the geometry and details of the interactions between these building blocks then control their copy numbers, positions and orientations within higher-order assemblies. We illustrate this strategy by creating planar rings of up to 350 nanometres in diameter and with atomic masses of up to 330 megadaltons, micrometre-long, thick tubes commensurate in size to some bacilli, and three-dimensional polyhedral assemblies with sizes of up to 1.2 gigadaltons and 450 nanometres in diameter. We achieve efficient assembly, with yields of up to 90 per cent, by using building blocks with validated structure and sufficient rigidity, and an accurate design with interaction motifs that ensure that hierarchical assembly is self-limiting and able to proceed in equilibrium to allow for error correction. We expect that our method, which enables the self-assembly of structures with sizes approaching that of viruses and cellular organelles, can readily be used to create a range of other complex structures with well defined sizes, by exploiting the modularity and high degree of addressability of the DNA origami building blocks used.
Pub.: 09 Dec '17, Pinned: 15 Jan '18
Abstract: Higher-order structures that originate from the specific and reversible DNA-directed self-assembly of microscopic building blocks hold great promise for future technologies. Here, we functionalized biotinylated soft colloid oil-in-water emulsion droplets with biotinylated single-stranded DNA oligonucleotides using streptavidin as an intermediary linker. We show the components of this modular linking system to be stable and to induce sequence-specific aggregation of binary mixtures of emulsion droplets. Three length scales were thereby involved: nanoscale DNA base pairing linking microscopic building blocks resulted in macroscopic aggregates visible to the naked eye. The aggregation process was reversible by changing the temperature and electrolyte concentration and by the addition of competing oligonucleotides. The system was reset and reused by subsequent refunctionalization of the emulsion droplets. DNA-directed self-assembly of oil-in-water emulsion droplets, therefore, offers a solid basis for programmable and recyclable soft materials that undergo structural rearrangements on demand and that range in application from information technology to medicine.
Pub.: 24 Nov '12, Pinned: 15 Jan '18
Abstract: DNA-based nanomachines are self-assembled DNA superstructures that harness chemical free energy to perform mechanical work. The development of DNA machines has benefited greatly from the achievements in both structural and dynamic DNA nanotechnology. In this review, the configurations of DNA machines, fuel systems, and operations are discussed to outline the evolving paths of DNA machines. The focus is on the smart mechanical behavior of DNA machines, from the standpoint of upgrading the complexity of DNA nanostructures, cooperative activation of multimachinary systems, and the establishment of a network of the mechanical states. In the end, the challenges are highlighted and possible solutions are proposed to push forward smart DNA nanomachines, with the goal of creating biomimicking systems. Insights are also provided into the potential applications of the DNA machines with designable intelligence.
Pub.: 19 Jun '13, Pinned: 15 Jan '18
Abstract: Abstract We developed a reaction system to generate multiple single-stranded DNA species at a physiological temperature for controlling the operation of DNA nanomachines. In this reaction system, cascading DNA generation is arbitrarily programmed by permutation and altering the combinations of template DNA sequences in a modular fashion. Because the dissociation of generated DNA strands from their templates is fully dependent on the strand displacement activity of DNA polymerase, generation and subsequent hybridization of DNA strands can be implemented in a one-pot reaction at the reaction temperature. We experimentally confirmed the generation and hybridization of DNA strands at a temperature remarkably lower than the melting temperature by monitoring the fluorescence change caused by the structural transition of molecular beacons as a simple DNA nanomachine operation. Then, we demonstrated the versatility and programmability of the cascading DNA generation up to three layers. By integrating the proposed DNA generation reaction with various types of DNA nanomachines, an intelligent molecular robotic system is expected to be achieved.AbstractWe developed a reaction system to generate multiple single-stranded DNA species at a physiological temperature for controlling the operation of DNA nanomachines. In this reaction system, cascading DNA generation is arbitrarily programmed by permutation and altering the combinations of template DNA sequences in a modular fashion. Because the dissociation of generated DNA strands from their templates is fully dependent on the strand displacement activity of DNA polymerase, generation and subsequent hybridization of DNA strands can be implemented in a one-pot reaction at the reaction temperature. We experimentally confirmed the generation and hybridization of DNA strands at a temperature remarkably lower than the melting temperature by monitoring the fluorescence change caused by the structural transition of molecular beacons as a simple DNA nanomachine operation. Then, we demonstrated the versatility and programmability of the cascading DNA generation up to three layers. By integrating the proposed DNA generation reaction with various types of DNA nanomachines, an intelligent molecular robotic system is expected to be achieved.
Pub.: 01 Jul '15, Pinned: 15 Jan '18
Abstract: Artificial DNA and RNA structures have been used as scaffolds for a variety of nanoscale devices. In comparison to DNA structures, RNA structures have been limited in size, but they also have advantages: RNA can fold during transcription and thus can be genetically encoded and expressed in cells. We introduce an architecture for designing artificial RNA structures that fold from a single strand, in which arrays of antiparallel RNA helices are precisely organized by RNA tertiary motifs and a new type of crossover pattern. We constructed RNA tiles that assemble into hexagonal lattices and demonstrated that lattices can be made by annealing and/or cotranscriptional folding. Tiles can be scaled up to 660 nucleotides in length, reaching a size comparable to that of large natural ribozymes.
Pub.: 16 Aug '14, Pinned: 15 Jan '18
Abstract: Realization of bioinspired molecular machines that can perform many and diverse operations in response to external chemical commands is a major goal in nanotechnology, but current molecular machines respond to only a few sequential commands. Lack of effective methods for introduction and removal of command compounds and low efficiencies of the reactions involved are major reasons for the limited performance. We introduce here a user interface based on a microfluidics device and single-molecule fluorescence spectroscopy that allows efficient introduction and removal of chemical commands and enables detailed study of the reaction mechanisms involved in the operation of synthetic molecular machines. The microfluidics provided 64 consecutive DNA strand commands to a DNA-based motor system immobilized inside the microfluidics, driving a bipedal walker to perform 32 steps on a DNA origami track. The microfluidics enabled removal of redundant strands, resulting in a 6-fold increase in processivity relative to an identical motor operated without strand removal and significantly more operations than previously reported for user-controlled DNA nanomachines. In the motor operated without strand removal, redundant strands interfere with motor operation and reduce its performance. The microfluidics also enabled computer control of motor direction and speed. Furthermore, analysis of the reaction kinetics and motor performance in the absence of redundant strands, made possible by the microfluidics, enabled accurate modeling of the walker processivity. This enabled identification of dynamic boundaries and provided an explanation, based on the 'trap state' mechanism, for why the motor did not perform an even larger number of steps. This understanding is very important for the development of future motors with significantly improved performance. Our universal interface enables two-way communication between user and molecular machine and, relying on concepts similar to that of solid-phase synthesis, removes limitations on the number of external stimuli. This interface, therefore, is an important step toward realization of reliable, processive, reproducible, and useful externally controlled DNA nanomachines.
Pub.: 14 Apr '17, Pinned: 15 Jan '18
Abstract: DNA strands of well-defined sequence are valuable in synthetic biology and nanostructure assembly. Drawing inspiration from solid-phase synthesis, here we describe a DNA assembly method that uses time, or order of addition, as a parameter to define structural complexity. DNA building blocks are sequentially added with in-situ ligation, then enzymatic enrichment and isolation. This yields a monodisperse, single-stranded long product (for example, 1,000 bases) with user-defined length and sequence pattern. The building blocks can be repeated with different order of addition, giving different DNA patterns. We organize DNA nanostructures and quantum dots using these backbones. Generally, only a small portion of a DNA structure needs to be addressable, while the rest is purely structural. Scaffolds with specifically placed unique sites in a repeating motif greatly minimize the number of components used, while maintaining addressability. This combination of symmetry and site-specific asymmetry within a DNA strand is easily accomplished with our method.
Pub.: 06 May '15, Pinned: 15 Jan '18
Abstract: Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure and a ~6000-nt RNA structure. We demonstrate facile replication of the strand in vitro and in living cells. The work here thus establishes unimolecular folding as a general strategy for constructing complex and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology.
Pub.: 16 Dec '17, Pinned: 15 Jan '18