Team: Aarhus University — Nano Creators
Title: Apoptosis served on an origami plate
Abstract: Our team, Nano Creators, have developed a DNA origami based nano drug that is designed to induce apoptosis in metastasizing cancer cells. Two origamis, a double-layered plate and a single-layered hemisphere, are connected through peptides containing a cleavage site for matrix metalloprotease 2, which is overexpressed by some actively metastasizing cancer cells. Thus, the structure will be opened within close proximity of the target cells and reveal its content. Two approaches have been developed. One with cholesterol conjugated to the plate enabling attachment to the cell membrane and facilitating the induction of apoptosis by photosensitizers, which produce singlet oxygen when irradiated by UV light. Another with cell penetrating peptides (CPPs) conjugated to small internally segmented interfering RNAs (sisiRNAs) linked to the plate through the cleavable peptide. Upon cleavage, the CPPs will transport the sisiRNAs into the cell where it induces apoptosis by selective gene knockdown through RNAi.
Team: Birla Institute of Technology and Science — Team BITSMOD
Title: Biomimetics at nanoscale: DNA origami to deliver IRES aptamers using HCV as a template
Abstract: With its worldwide distribution, Hepatitis C Virus (HCV) infects about 3-4 million people every year of which the chronically infected ones are at a risk of developing liver cirrhosis, hepatic failure or hepatocellular carcinoma. The limited availability and poor tolerance towards antiviral therapy and interferon with ribavirin (nucleoside inhibitor) demands a different approach towards targeting the HCV infection. Research indicates that the HCV genome translation is under the control of the Internal Ribosomal Entry Site (IRES) which mediates cap-independent internal initiation of HCV polyprotein translation thereby making it a quintessential target to halt and thereby curb the infection. Nucleic acid ligands generated using SELEX (Systematic Evolution of Ligands by EXponential enrichment) called aptamers, are the recent class of molecules showing immense potential to be crafted for binding to multiple different targets. First proposed by Seeman and started by Rothemund, DNA origami is based on the principle that a long ssDNA scaffold can be molded into any desired shape using staples. With this method of tailoring DNA nanostructures, the self assembling property of nucleic acids would be exploited for the delivery of IRES specific aptamers to the HCV infected cells. We designed a cylindrical nanostructure mimicking HCV by attaching E1-E2 conjugate peptide sequences, facilitating the entry via endosomal pathway; and by using pH sensitive detachable lids to release the IRES aptamers packed inside the nanostructure to the infected cells. The aptamer based silencing of viral translation will in turn prevent the assembly of new viroids and serve as a mechanism to control the HCV infection.
Team: Boston University — Terriergami
Title: BrainBots: Targeting DNA Nanostructures to Brain Cells Using a Peptide Conjugation Strategy
Abstract: The DNA origami technique allows the creation of nanostructures of intricate shapes; however these particles have no intrinsic cell targeting ability. Using a novel functionalization strategy, targeting peptides can be displayed from the helix ends of DNA nanostructures allowing a controlled number of bioactive signals to be presented in a polyvalent fashion. DNA origami structures were functionalized with peptides that are blood-brain permeable as well as those that selectively bind neurons, with the goal of targeting nanoparticles into the brain following injection into the bloodstream. It is envisioned that this technology can be useful for therapy or diagnostics for many neurological and psychiatric disorders.
Team: Columbia University — Dynein Dynasty
Title: Enzymers: The polymerization of functional enzyme chains
Abstract: Enzymes are the catalysts to every chemical reaction that allows for the existence of life. In nature, many chemical reactions are coupled, with the product of one reaction being used as the reagent for another nearby enzyme. The aim of this project is to couple Glucose Oxidase and Horseradish Peroxidase, an enzyme pair used in spectrophotometer assays, using azide-alkyne click chemistry via NHS ester conjugation. Increased efficiency and yield of a coupled reaction would have tremendous impact on the field of chemical creation and chemical purchases.
Team: Columbia University — NanoMechanists
Title: Assembly of DNA nanostructures to create a targeted drug delivery system
Abstract: DNA origami, the art of folding single stranded DNA scaffolds with approximately 200 shorter oligonucleotide staples into desired multi-planar shapes, provides a method by which a payload can be contained within a structure of highly specific configuration. This study demonstrates the assembly of three independent origami structures of m13mp18 viral DNA scaffold, forming a single systematic complex. Two parts join to form a securely closed capsule, with a basket weave pattern crisscrossing their respective outer ends -- this section contains scaffolds and staples running perpendicular crossing at 6 nt intervals, effectively blocking anything from entering or leaving the capsule. The two part capsule design may also allow for in-vivo quantitation of opened vs. closed structures. The third part of this capsule system is a dense inner core structure which can be used as a sponge to absorb drugs such as chemotherapeutics. The energetic barrier for assembling these structures will be addressed using a series of hybridizing oligos which act as toeholds. Once these capsules are assembled they may be secured using a system of aptamers, which can later be conditionally released. The drug payload absorbed inside the bundle structure remains enclosed within the capsule until the designated release point is near. We envision this nano-capsule design as a safer and targeted drug delivery method for existing drugs which would otherwise produce excessive collateral damage.
Team: Fukuoka Institute of Technology — Team Fukuoka
Title: The DNA weathercock mounted on a porous substrate
Abstract: We fabricate the "DNA-weathercock" mounted to the nano-pore of an inorganic substrate: the weathercock freely rotates and points to the direction of the surrounding liquid flow, finally outputting the fluorescence signal. Based on the DNA origami technology, we synthesize the DNA-weathercock which is consist of the shaft part, the blade part, and a fluorescence molecule. As the platform to mount the weathercock, we use the anodizing alumina substrate that has the regularly arranged nano-pores with the tunable inner-diameter of 6-30 nm. We mount the weathercock shaft into the nano-pore of the inorganic substrate, so that the weathercock can freely rotate and points to the flow direction. The flow direction is finally detected by polarized fluorescence microscopy. Our approach that combines DNA-origami and inorganic nanomaterial would be a good general solution for easy integration of movable parts in the DNA-origami-based devices at a reduced cost.
Team: Hokkaido University— Hokkaido-U MARIMOD
Title: Bio “MARIMO” MOLECULES
Abstract: Biomolecular motor system such as microtubule-kinesin is an example of smallest natural machine that can convert chemical energy obtained from ATP into mechanical work with high efficiency and specific power. Nowadays microtubule-kinesin system is being used as a building block for constructing micro-actuators and driving unit of the biodevices. Kinesin converts chemical energy derived from the hydrolysis of ATP molecules into directed, stepwise motion along microtubule. In the closed system, microtubule-kinesin system consumes ATP, and this cause kinesin to stop. Development of a system to provide energy continuously is highly desired. On the other hand, F1-F0 ATP synthase, another biomolecular motor exists in the thylakoid membrane, works together with photosystems and is known to play important role in ATP generation. Incorporate this ATP generating system into microtubule-kinesin system would allow kinesin to work for longer period. To achieve this, we prepared the thylakoid membrane-supported spherical gel which is termed as “Marimo-gel”. The name “Marimo” means moss ball in English and marimo is one of the most representative plants of Hokkaido. By exposing light on to the Marimo-Gel, synthetic ATP would be supplied. This biomolecular-based ATP reproduction system has potential to be a long-term working device without energy depletion.
Team: Hong Kong Baptist University — The Rising Power
Title: Quantum Dot-Functionalized DNA Origami Serves as Effective Biomolecular Sensors on a Protein Nanofibril Platform
Abstract: DNA origami has enabled manipulations of sophisticated nanoscale constructions; however, the biomedical applications of DNA origami are not yet well explored. Quantum dots (QD) are well-known for their photostability and unique physical properties; they can be visualized individually through fluorescence microscopy. Previous work demonstrates the spontaneous attachment of QD onto self-assembling amyloid fibrils. In this project, self-assembling DNA origami modified with biotins was conjugated to streptavidin-QD625, and then the complex was aligned spontaneously onto biotinylated beta-amyloid fibrils. Each of the fibrils was clearly monitored under both fluorescence microscope and atomic force microscope, illustrating the effective attachment of QD-functionalized DNA origami on a well-defined self-assembling protein fibril. The whole as-prepared complex is ready to be served as biosensor for specific target molecules when a probe is attached to the QD. It is of high potential for development in biocompatible nanomaterials to detect cellular and molecular components, which advance clinically disease diagnosis.
Team: Indian Institute of Technology, Madras — Acid Artists
Title: Environmentally Triggered DNA Systems
Abstract: DNA nano-structures have proved to be very effective tools in solving Structural Biology and Biophysics problems, with potential applications in fields such as Nano-medicine. However, since it may not always be desirable to have functioning nano-structures in a given system, a structure which folds into an appropriate configuration based on specific triggers would be more useful. The strand exchange system for actuating DNA nano-structures results in the generation of dsDNA waste products that increase the systems’ toxicity. The time-scale of system response is extremely high owing to diffusional limitations. An exciting alternative to this technique is the use of environmental triggers (such as pH, temperature, light). This reduces the response time and results in spatio-temporal homogeneity of system response. As there is no addition of any synthetic intermediate, the system is comparatively “Clean”. Our project is a proof-of-concept demonstration of an environmentally triggered DNA nano-structure – specifically, a DNA walker activated by a pH change. This pH-based construct has been designed using a single strand of DNA rich in Cytosine repeats which undergoes a conformational change at a low pH, releasing a walker strand from its bound configuration onto a neighboring strand present on the track. This system is a putative candidate for probing systems with varying pH, notably cancer and tumor cell systems.
Team: Ludwig-Maximilians-Universität — DNA Diamonds
Title: Site-specific assembly of fluorescence nanodiamonds on DNA-origami
Abstract: Over recent years, fluorescent nanodiamonds moved into the focus of nanophotonic research due to their unique optical properties. Nanodiamonds possess excellent photostability and exhibit remarkable quantum-physical behavior. Their surfaces are accessible to chemical functionalization and their biocompatibility and nontoxiticity predestine them for future in vivo studies. So far, nanodiamonds have been utilized in various applications such as biolabeling, single-particle-tracking, or single-photon experiments. Nevertheless, a controlled arrangement of nanodiamonds is required to provide addressable structures and to ultimately perform quantum-information experiments. DNA origami provides a bottom-up technique to easily create 3D shapes of basically any geometry, which in turn would allow for the nanoscale arrangement of DNA-functionalized nanodiamonds. With this aim in mind we developed a biocompatible coating strategy to functionalize the diamonds surface in order to attach them to specific sites on DNA origami structures. Proper placement of the functionalized nanodiamonds was verified via TEM and AFM measurements. We expect our assemblies to open the route for both fundamental quantum-mechanical studies and biological applications with fluorescent nanodiamonds.
Team: Massachusetts Institute of Technology — Self-Assembly Lab
Title: DNA DisPLAY
Abstract: This project attempts to take-on the challenge of DNA design by making DNA both physical and visual as a new creative medium. We aim to allow anyone to design with DNA by using easy and powerful software tools with direct ordering of custom DNA sequences and a new process for CNC printing DNA images on paper. This project eliminates the expensive and difficult process of imagining, order and DNA handeling for non-experts. In the near future, we imagine that DNA patterns can become microfluidic, diagnostic and electronic displays where the structure of the drawing becomes a computational medium.
Team: North Carolina State University — Team DNAbeans
Title: Macroscale Ordering of Asymmetrical Heterodimers
Abstract: Ordering particles is difficult on the nanoscale and unfortunately becomes harder on larger length scales. Assembling particles on greater length scales allow for the design of structures with finely tuned properties not to mention precise arrangements. To accomplish macroscale ordering of nanoscale particles, one can either construct an ordered array via controlled assembly and placement; requiring fine-tuned reactions and kinetics resulting in a difficult game of nanoscale tetris, or by arranging the particles after their creation into an ordered array. While the first method requires precise control over the reactions and kinetics of the particles the second method allows for a less sensitive procedure. Using heterodimers composed of gold nanorods and quantum dots linked together with an oligonucleotide we hope to create a macroscale ordered array to exploit the plasmonic properties of gold nanorods on a higher length-scale. A recent paper demonstrated the alignment of gold nanorods suspended within a polymer (PEO) parallel to the axis of the electrospun polymer fibers. By electrospinning our heterdimer’s in Su-8 we hope to align our particles within the fibers to create a macroscale array of nanoscale heterodimers. This alignment will allow us to exploit the plasmonic properties of the gold nanorods on a higher length-scale than previously possible.
Team: Seoul National University — Lab-on-a-Lipid Bilayer
Title: In Situ Manipulation of Dynamically-Tethered DNA Origami Nanostructures on Supported Lipid Bilayer
Abstract: DNA origami nanostructures have been used as highly versatile nano breadboards for the single-molecule analysis of many chemical and biochemical processes and for the precise positioning of various functionalities. Previously, binding events on DNA origami templates have been visualized by atomic force microscopy and electron microscopy that typically provide the static information without in situ data and require complicated procedures under harsh conditions. Here, we developed a novel method for in situ imaging and analysis of the interactions between DNA nanostructures and plasmonic nanoparticles (PNPs). The key strategy was to tether DNA origami nanostructures and PNPs on diffusible 2D supported lipid bilayer (SLB). The movements of DNA nanostructures tagged with AuNPs were individually controlled and tracked under dark-field microscopy as they were confined in the 2D focal plane of the microscopy. This platform, depending on the molecular reactions to mediate the interactions, can be utilized for the development of multiplexed DNA detection assay and the real-time study of successive chemical reactions at the single-molecule level. In our future research, we plan to further develop this platform into a cell membrane-mimicking simulator used for designing autonomous DNA nanorobots with novel biological activities.
Team: St. John's University — Toehold Conga Nanny
Title: Virus-Binding Origami 'Claws'
Abstract: The goal of this project is to design and characterize a DNA origami (DO) structure that undergoes significant conformational changes when bound to objects ranging in size from 10-100 nm. Since binding-specific conformational change can be transduced into a signal, this should enable the design of nanometre-scale sensors for viruses. In our proof-of-principle approach, the origami structure is a three-pronged DO ‘claw’ with sticky-ended DNA strands complementary to the surface of a modified bacteriophage MS2 capsid substrate. We characterize this binding by gel shift, AFM and DLS. We also describe selection approaches to claw isolation, the beginnings of making more realistic virus-surface binding units and the generation of rigid triangular 'struts' that can be embedded into DNA origami.
Team: The Ohio State University — Team OhioMOD
Title: Overcoming Drug Resistance in B-Cell Malignancies Using Intercalating Drug Loaded DNA Nanostructures
Abstract: Approximately 150,000 Americans will be diagnosed with B-cell malignancies in 2013. Although treatment strategies exist, the disease is incurable due to development of drug resistance demanding novel therapeutic approaches. DNA origami nanostructures loaded with intercalating drugs were reported to circumvent drug resistance in MCF-7 breast cancer cells. We build on these results to evaluate how design parameters affect drug-loading efficiency and cytotoxicity in HL-60 drug resistant human B-cells. Here, 6-,12-, and 18-helix bundle honeycomb lattice structures, and a square lattice-based 16-helix bundle loaded with the intercalating drug daunorubicin were employed to evaluate whether surface area, density, or lattice conformation affected drug-loading efficiency and cytotoxicity. The 6-,and 12-helix bundles, and square 16 helix bundle had the highest loading efficiency, while daunorubicin-loaded 16-helix bundles most effectively killed drug resistant HL-60 cells suggesting surface area and lattice structure are critical for cytotoxicity. Future studies will evaluate structure cellular uptake and targeting via antibodies.
Team: The University of Texas at Austin — NanoHack
Title: Split-catalyst catalyzed hairpin assembly: A novel method for the detection of single nucleotide polymorphisms and apurinic sites
Abstract: Obtaining quick and accurate diagnostic test results is vital for effective treatment of patients. Point-of-Care (POC) diagnostics function to decrease physician dependence on amply-equipped medical laboratories, thereby expediting the delivery and reducing costs of routine testing. While many POC diagnostics detect small molecules, specific detection and characterization of genomic material remains largely reliant upon enzymatic methods with extensive resource requirements for both assay interpretation and reagent support. The superior stability of nucleic acids to enzymes and the programmable nature of nucleic acid hybridization events make nucleic acids good candidates for the development of rugged and accurate POC diagnostics. Catalyzed hairpin assembly (CHA) is an enzyme-free nucleic acid signal amplification circuit that enables specific detection of oligonucleotides. In this work, we present the development of a modified version of CHA, herein referred to as split-catalyst CHA (scCHA), for discrimination of cancer-linked single-nucleotide polymorphisms in the human MDM2 gene and ricin-generated ribosomal apurinic sites.
Team: The University of Tokyo Kashiwa — Todai nanORFEVRE
Title: Oligomeric Cell Killer: Cancer-Specific Pore-Forming DNA Origami Drug
Abstract: Cancer is one of the most common diseases in the world. Chemotherapy is a popular treatment for cancer, however, it attacks normal cells in addition to cancer cells, causing severe side effects in some cases. Recently drug delivery system (DDS) has developed to improve cancer-specificity, but it is difficult to optimize delivery system for each drug. Here, we tried to make a prototype of oligomeric cancer specific pore-forming DNA origami, termed Oligomeric Cell Killer (OCK), which might be a side effects free anti-cancer drug. OCKs exist in a monomeric form in solution and penetrate into the cell randomly. Cancer specific molecules on the membrane of cancer cell trigger the oligomerization of OCK, resulting in the pore-forming and subsequent death of cancer cell. In contrast, the OCKs keep monomeric form in the normal cell, allowing the normal cell to keep alive. Our study might be the basis for cancer specific drug. (150 words)
Team: The University of Tokyo Komaba — Team UT-Komaba
Title: DNA screw, a rotary molecular motor
Abstract: DNA-based molecular motor engineering is a sprouting field that is expected to have promising outcomes. Even so many approaches have been carried out, rotational movement seems to have been neglected. Our purpose is to realize such rotary motion in nanoscale. To make a concrete rotational motion, we develop the DNA Screw, a 3-part motor which combines 2 well-known DNA nanotechnologies: the DNA origami is used to create a cylinder and a ring, making the core of the motor. Then, the movement process relies on DNA walkers. The walkers are bound to the ring and run along the cylinder following a track set out spirally on the cylinder's side. Rings and cylinders are assembled by DNA-origami technology, which enables us to embed DNA Screws into other DNA structures easily. The rotational motion in the nanoscale world contributes to many applications, and the DNA Screw expands the possibilities of DNA engineering.
Team: Tianjin University — Team Tianjin
Abstract: This year our project is to build a DNA walker device that can build its track by itself. We first build a DNA origami, and we try to conjugate the origami with two DNA strands which have special functions. The first kind of DNA is a DNA walker linked to a specific DNA which is a substrate of a DNAzyme. The walker is made of DNAzymes. The other kind of DNA can catalyze two different stem-loop shaped DNA to have a polymerizing reaction. When we put the origami into the solution of the stem-loop shaped DNA, the DNA begin to polymerize from the origami, and form as a track. If we add the DNAzyme into the solution and release the walker, the walker will walk along the track(polymer) to anywhere we want it to be. This mechanism is hopeful to be used in drug deliver system.
Team: Tohoku University — Team Sendai
Abstract: We are aiming at constructing a chain-reactive molecule-releasing system in this project. In living organisms, signal transduction is widely used in many situations. Here we construct a signal transduction-like system through an approach of DNA nano-engineering. In our project, trigger DNAs and payload molecules are encapsulated in a liposome. The trigger DNA is specially designed to collapse the liposome when some initiation stimulus is applied. Once one of the liposomes collapsed, the trigger DNAs are released from the liposome and that break other liposomes in chain-reactive fashion. This mechanism of “chain-reactive burst” enables us to release a large amount of payload molecules all at once, driven by a faint trigger signal. We believe this system offers a fundamental technique of signal transduction/amplification of various kinds of chemical or physical signals, applicable to Drug Delivery System, molecular computers and so on.
Team: Tokyo Institute of Technology — Team Platanus Symphony
Title: Cosmetic Biomolecular System ~meets individuals’ needs~
Abstract: Recently, numerous biomolecular devices have been developed and they are expected to be integrated into intelligent molecular systems. Usually, these systems are designed to attain fixed outcomes, for example, a cure of disease. However, the conventional design principle, in which engineers settle the target outcomes, can not deal with the problems of which the best answers differ among people, such as beauty, fashion, love, etc. Here, we propose a cosmetics-oriented biomolecular system for aiming at expanding the relationship between users and engineers in biomolecular systems design. The present system has two functions. In the “UV-Tuning Nano-Parasol” function, our system as a cell-scale sunshade autonomously keeps the level of suntan according to the user-defined threshold of UV exposure. In the “Colorful Makeup” function, a user can choose and easily change a variety of structural colors according to TPO. Our molecular system introduces the higher order of flexibility to biomolecular systems engineering.
Team: TU Dresden — Dresden Nanormous
Title: Enzyme-containing and antibody-directed smart nanoreactors based on pH responsive polymer spheres with a DNA-origami-based import and export system.
Abstract: In recent years DNA origami reached incredible popularity in nanotechnology due to its vast design possibilities and its broad potential applications. While having numerous advantages it is still exceptionally expensive to produce in high amounts for mass applications, whereas inorganic polymers, another range ofmaterials available for biomolecular design can compensate for this disadvantage. Nowadays they can be found in almost every aspect of our lives, in medicine and technology through their wide range of different functionalities and their moderate price. In our project we aim to combine those two artificial materials into one device: functional and responsive polymers as carrier material with highly flexible designable DNA origami for more complex access points to gain the best of both of them: to create a smart nanoreactor. We aim to build two different hollow spheres out of block copolymers PEG-b-P(DEAEMA-stat-BMA) and PMOXA-PDMS-PMOXA, one being pH responsive whereas the latter being pH stable and to combine them with channels of DNAorigami to facilitate transport in and out of our spheres. Additional functionalization of the polymer surface with antibodies and encapsulation of enzymes inside the spheres complete our assembly to create a smart nanoreactor with a wide range of applications in medicine and technology.
Team: Universidad Autónoma de Nuevo León — Team NanoUANL
Title: A model for silver nanoparticle synthesis by enzimatic reduction of silver ions in a protein cage
Abstract: Although Ag-NP synthesis has been widely studied, the variables involved, such as substrate intake, enzymatic activity and atomic nucleation of silver, vary on a nanometric scale and within a specific geometry, which is of great interest. Our proposed model for Ag-NP synthesis involves constrained growth inside a modified viral capsid, aided by the enzyme HRP. A simplification of the system as a series of simple, more accessible scenarios is needed for computational analysis. Through the use of a variety of computer programs and algorithms for many-body problems (such as Monte Carlo), we expect to obtain a model to describe this phenomenon with more detail as a basis for future novel applications in the field of material synthesis.
Team: University of Waterloo — Team UW-DNA
Title: A nanomanufacturing system capable of synthesizing small quantities of multifunctional nanoparticle-DNA conjugates
Abstract: The goal of the uwDNA student engineering design team for the Biomod 2013 competition is to produce, using the DNA origami technique, a working nanomanufacturing system capable of synthesizing small quantities of nanoparticle-DNA conjugates from quantum dots, iron oxide nanoparticles, and gold nanoparticles. Our work is based on a paper by Gu et al published in Nature in May 2010 where a team of researchers created a nanomanufacturing system that synthesized gold nanoparticle-DNA conjugates in a controlled manner. Through characterization techniques including transmission electron microscopy, gel electrophoresis, and atomic force microscopy, uwDNA will demonstrate that the system is capable of combining the three types of nanoparticle cargoes available into one structure.
Team: Xiamen University — Team Nanobiocat
Title: Assembly of multi-enzyme biomolecular machines for Bio-tattoo
Abstract: A safe and easy way to perform bio-tattoo by DIY tanning is promoted. Dihydroxyacetone (DHA), the most effective additive for sun-free tanning as an alternative to UV tanning, is biosynthesized in situ from glycerol by designed biomolecular machines. Based on dynamic simulation, the site-to-site oriented biomolecular machines assembling was triggered by metal ions. The coupling multi-enzyme system, glycerol dehydrogenases (GDH) and NADH oxidase (NOX) enzyme nanoring, catalyze the biosynthesis of DHA coupling with NADH regeneration. Biomolecular machines efficiency varies with the concentration of NADH and glycerol. Multi-enzyme nanoflowers were formed with the co-precipitated of quaternary ammonium and GDH-NOX. The integration brings antibacterial activity and enhances enzyme activity and stability. Coloration levels from light to dark correspond with the DHA percentages. Various patterns and letters can be printed on the skin using packs, providing a safe, painless and easy handling way for DIY bio-tattoo.