[nihila]

DNA nanotechnology is broadly divided into two branches - Structural and Dynamic DNA nanotechnology.

What is Nanotechnology?
Nanotechnology is the field of science and technology which is concerned with studies of substances and systems at the atomic and molecular level which is generally 100 nanometers or smaller. It is a rapidly developing field, the societal implications of which are already evident. And DNA nanotechnology is branch which aims to create novel, controllable nanostructures out of DNA by using its unique molecular recognition properties and to achieve molecular self-assembly through the manipulation of DNA. It is a technology in which molecular components spontaneously organize into stable structures; this form of structures is induced by the physical and chemical properties of the components selected by the designers. These components have strands of nucleic acids such as DNA, which are constructed in nanoscale as a nucleic acid double helix has a diameter of 2 nm and a helical repeat length of 3.5 nm. The most important property of nucleic acids is that the binding between two nucleic acid strands depends on simple base pairing rule which helps in assembly of nucleic acid structures easy to control through nucleic acid design. This technology is used in manufacturing of various nanomedicine which is used for various treatments of various diseases. It is helping scientists and researchers in creating synthetic vaccines that could one day help treat and prevent many potentially fatal diseases like cancer, AIDS, Hepatitis, influenza, etc.

DNA nanotechnology has two broadly divided branches-

One is Structural DNA nanotechnology (SDN) which focuses on synthesizing and characterizing nucleic acid complexes and materials that assemble into a static, equilibrium end state. It uses unusual DNA motifs to build target shapes and arrangements and these are generated by reciprocal exchange of DNA backbones, leading to branched systems with many strands and multiple helical domains. The motifs may be combined by sticky ended cohesion, involving hydrogen bonding or covalent interactions and other forms of cohesion involves edge-sharing or paranemic interactions of double helices. Some of these motifs are simple branched junctions, but other motifs represent more complex strand topologies, with greater structural integrity. Other than this double crossover (DX), triple crossover (TX), paranemic crossover (PX) and parallelogram motifs are of great use. The sequences of these unusual motifs are designed by an algorithm that attempts to minimize sequence symmetry. A core goal of DNA nanotechnology is the self-assembly of periodic arrays. Micron-sized 2-dimensional DNA arrays from DX, TX and parallelogram motifs can be constructed. Patterns can be changed by changing and modifying the components after assembly. DNA molecules have been used successfully in DNA-based computation as molecular representations of Wang tiles, who’s self-assembly can be programmed to perform a calculation.

The other is Dynamic DNA nanotechnology which focuses on creating nucleic acid systems with designed dynamic functionalities related to their overall structures, such as computation and mechanical motion. Some complexes have a combination of both the subfields such as nucleic acid nanomechanical devices. DNA complexes change their structure with change in some stimulus, making them one form of nanorobotics which is designed to have a dynamic reconfiguration after the initial assembly. Various devices like circuits, catalytic amplifiers, autonomous molecular motors and reconfigurable nanostructures have been designed to use DNA strand-displacement reactions where two strands with partial or full complementarity hybridized by displacing one or more pre-hybridized strands. This mechanism allows for the kinetic control of reaction pathways and buffer is required. Some systems can change with the change in control strands thus forming multiple devices which independently operate in buffer solution. Cascades of strand displacement reactions can be used for either computational or structural purposes and are energetically favorable through the formation of new base pairs, and the entropy gain from disassembly reactions. These cascades are conducted under isothermal conditions for the assembly or computational process. They can also support catalytic functionality of the initiator species, where less than one equivalent of the initiator can cause the reaction to go to completion. These strand displacement complexes are used to form molecular logic gates capable of complex computation and these molecular computers use the concentrations of specific chemical species as signals. In nucleic acid strand displacement circuits the signal is the presence of nucleic acid strands that are released or consumed by binding and unbinding events to other strands in displacement complexes.

[BojanaL]

Application of DNA nanotechnology

First synthetic material made of nucleic acids is created in 1991 and since then, variety of produced DNA materials is growing unstoppably. Application of DNA nanomaterials increased greatly also. It is estimated that bionanotechnology market will grow up to 6 billion of dollars by 2017. DNA nanomaterials are helpful in crystallography (identification of structures of various materials), in NMR spectroscopy, in synthetic chemistry and in biophysics. However, the most important application of DNA nanomaterials is in the field of nanomedicine, more specifically in the cancer treatment.

Cancer is a widespread and incurable disease. Although latest medical approaches and newly synthesized drugs can prolong life expectancy of cancer patients, ideal weapon against cancer still needs to be developed. Chemotherapy is most commonly used therapeutic approach where one or more antineoplastic agents will be delivered to the patients. These agents target fast dividing cells, but unfortunately can’t distinguish between cancer dividing cells and those that are normally dividing in the fast manner, such as bone marrow cells, hair cells or cells in our intestines….That is why people lose their hair and experience some unpleasant side effects such as myelosuppression and mucositis (inflammation of the lining in the digestive tract). Radiation and surgery are often combined with chemotherapy, but even with all these techniques, cancer eventually wins the battle.

Fast growing field of nanomedicine offered some new techniques and methods that could be more beneficial and less painful for the cancer patients. These are associated with targeted delivery of cancer drugs and induction of apoptosis in the cells that should be eliminated from the body. Idea of “magic bullet” (targeted delivery, where only causative agent of disease is destroyed) is old, but it had to be postponed until an ideal nanomaterial was designed. DNA origami folding was invented in 2006: single stranded DNA is folding while numerous smaller DNA chains are attaching to it, forming 2- or 3D structure or various sizes and shapes (from smiley faces to cubes). This model proved to be very efficient in targeted drug delivery because it can hold drug and release it only under certain circumstances (proteins, DNA or RNA in the target cells will trigger drug release).

Group of scientists from Sweden recently created DNA origami model that could deliver precise amount of doxorubicin to the breast cancer cells. Doxorubicin induces intercalation of the DNA molecule (it inserts itself between nuclear bases) and prevent replication of DNA and further cell division. Unfortunately, this antineoplastic agent can affect DNA of healthy cells and thus it is very important to find a way to deliver it specifically to the affected cells and induce targeted destruction of the harmful cells. In the mentioned model of drug delivery, scientists tested global twisting of the origami DNA combined with releasing rate of the drug. They managed to design optimally twisted nanostructure that provides ideal drug release kinetics. Experiment showed that doxorubicin delivered in small amount (but at the precise location) induces better effect in cancer destruction than free doxorubicin, when deliver via classic route.

Another, even more impressive approach showed that cancer cells can be destroyed without well known drugs. Group of scientists from Harvard’s Wyss Institute developed a barrel-like robotic device (origami DNA is the basic structure) that could target and command destruction of cancer cells using simple molecular mechanisms that our body normally uses when it fights against foreign bodies. Just like in “classic” drug delivery system, their device was equipped with cargo, but instead of drug, it was filled with antibodies that could recognize and attach to the cancer cells and induce programmed cell death (apoptosis) by triggering molecular cascade. They tested efficacy of the newly developed model using leukemia and lymphoma cells. Since they belong to a different cancer types, they created different types of antibodies to serve as messengers of apoptosis. Signal for release of payloads were proteins on the surface of the cancer cells. Effective and quick release of the payload was possible due to specific shape of the device (open barrel). Success achieved with this experiment convinced scientists that they can expand list of diseases that could be treated using this method. Simple shape of the device allows fast release of antibodies (that should match various targeted cells) and further facilitates idea of targeted apoptosis in different diseases.

Thanks to rapidly growing field of nanomedicine, fight against cancer is almost over.