Showing posts with label DNA nanotechnology. Show all posts
Showing posts with label DNA nanotechnology. Show all posts

October 04, 2014

RCas9: A Programmable RNA Editing Tool

[Lawrence Berkeley National Lab] A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA, the molecule that translates DNA’s genetic instructions into the production of proteins. A team of researchers with Berkeley Lab and the University of California (UC) Berkeley has demonstrated a means by which the CRISPR/Cas9 protein complex can be programmed to recognize and cleave RNA at sequence-specific target sites. This finding has the potential to transform the study of RNA function by paving the way for direct RNA transcript detection, analysis and manipulation.

Led by Jennifer Doudna, biochemist and leading authority on the CRISPR/Cas9 complex, the Berkeley team showed how the Cas9 enzyme can work with short DNA sequences known as “PAM,” for protospacer adjacent motif, to identify and bind with specific site of single-stranded RNA (ssRNA). The team is designating this RNA-targeting CRISPR/Cas9 complex as RCas9.

Schematic shows how RNA-guided Cas9 working with PAMmer can target ssRNA for programmable, sequence-specific cleavage.

Nature - Programmable RNA recognition and cleavage by CRISPR / Cas9

April 08, 2014

Summarizing DNA nanotechnology, Synthetic Biology are on the path to realizing visions of nanomedicine and Nanoscale Metamaterial to visible spectrum control

DNA nanotechnology, synthetic biology and nanoscale metamaterials are on the path to realizing visions of nanomedicine and visible spectrum control.

DNA nanorobotics and synthetic biology are the first two items. One thing to remember is that work that is published in research papers was done in the lab 1-2 years ago. The current work by the
researchers is ahead of what they published. The third item is metamaterial related. The actual application of stationary cloaking in the visible spectrum is less interesting that the large scale
production of nanoscale feature size metamaterials which can be adapted to engineer physical properties. One point of interest in the second item beyond determining how to reinforce DNA structures was the DNA paint capability to enhance observation at the nanoscale.

DNA nanorobots are demoed in live cockroaches and could be in humans by 2019 and could scale to Commodore 64 - eight bit computing power

1. Researchers have injected various kinds of DNA nanobots into cockroaches. Because the nanobots are labelled with fluorescent markers, the researchers can follow them and analyse how different robot combinations affect where substances are delivered. The team says the accuracy of delivery and control of the nanobots is equivalent to a computer system.

This is the development of the vision of nanomedicine.
This is the realization of the power of DNA nanotechnology.
This is programmable dna nanotechnology.

DNA origami nanorobots shown in demo of drug delivery in live cockroaches with hope of human trials by 2019 and scaling DNA nanobot computing to Commodore 64 levels

Researchers have injected various kinds of DNA nanobots into cockroaches. Because the nanobots are labelled with fluorescent markers, the researchers can follow them and analyse how different robot combinations affect where substances are delivered. The team says the accuracy of delivery and control of the nanobots is equivalent to a computer system.

This is the development of the vision of nanomedicine.
This is the realization of the power of DNA nanotechnology.
This is programmable dna nanotechnology.

The DNA nanotechnology cannot perform atomically precise chemistry (yet), but having control of the DNA combined with advanced synthetic biology and control of proteins and nanoparticles is clearly developing into very interesting capabilities.

"This is the first time that biological therapy has been able to match how a computer processor works," says co-author Ido Bachelet of the Institute of Nanotechnology and Advanced Materials at Bar Ilan University.

The team says it should be possible to scale up the computing power in the cockroach to that of an 8-bit computer, equivalent to a Commodore 64 or Atari 800 from the 1980s. Goni-Moreno agrees that this is feasible. "The mechanism seems easy to scale up so the complexity of the computations will soon become higher," he says.

An obvious benefit of this technology would be cancer treatments, because these must be cell-specific and current treatments are not well-targeted. But a treatment like this in mammals must overcome the immune response triggered when a foreign object enters the body.

Bachelet is confident that the team can enhance the robots' stability so that they can survive in mammals. "There is no reason why preliminary trials on humans can't start within five years," he says

Biological systems are collections of discrete molecular objects that move around and collide with each other. Cells carry out elaborate processes by precisely controlling these collisions, but developing artificial machines that can interface with and control such interactions remains a significant challenge. DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems, logic circuits and robotics. The molecule also interfaces naturally with living systems, and different forms of DNA-based biocomputing have already been demonstrated. Here, we show that DNA origami can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof of principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT and a half adder). Following an ex vivo prototyping phase, we successfully used the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets their cells.

Nature Nanotechnology - Universal computing by DNA origami robots in a living animal

April 04, 2014

Eric Drexler Counts Five kinds of nanotechnology and two are not called nanotechnology currently

Eric Drexler counts five kinds of nanotechnology, of which only three are called by that name. Of the three, one is a revolutionary prospect, one is a fantasy, and the third is mostly materials science. As for the other two kinds, one is the heart of today’s greatest technological revolution, while the other is the basis for progress toward the revolutionary prospect — but neither of these is called “nanotechnology”.

Synthetic Biology and DNA Nanotechnology would be under molecular design and synthesis but also possibly Atomically Precise Manufactuing in some cases.

April 03, 2014

DNA origami make sturdier polyhedra with struts to get them 400 times larger than DNA bricks

Scientists at the Harvard's Wyss Institute have built a set of self-assembling DNA cages one-tenth as wide as a bacterium. The structures are some of the largest and most complex structures ever constructed solely from DNA. The cage could be modified with chemical hooks that could be used to hang other components such as proteins or gold nanoparticles. With sides of 100 nm length, and a volume one one thousandth that of a typical bacterial cell, these ‘closets’ should be large enough to precisely assemble fairly complex assortments of nanoscale functional elements.

The scientists visualized them using a DNA-based super-resolution microscopy method — and obtained the first sharp 3D optical images of intact synthetic DNA nanostructures in solution.

In the future, scientists could potentially coat the DNA cages to enclose their contents, packaging drugs for delivery to tissues. And, like a roomy closet, the cage could be modified with chemical hooks that could be used to hang other components such as proteins or gold nanoparticles. This could help scientists build a variety of technologies, including tiny power plants, miniscule factories that produce specialty chemicals, or high-sensitivity photonic sensors that diagnose disease by detecting molecules produced by abnormal tissue.

The five cage-shaped DNA polyhedra here have struts stabilizing their legs, and this innovation allowed a Wyss Institute team to build by far the largest and sturdiest DNA cages yet. The largest, a hexagonal prism (right), is one-tenth the size of an average bacterium. Credit: Yonggang Ke/Harvard's Wyss Institute

Science - Polyhedra Self-Assembled from DNA Tripods and Characterized with 3D DNA-PAINT

March 25, 2014

Cadnano simplifies and enhances the process of designing three-dimensional DNA origami nanostructures

Shawn Douglas is an advocate for Cadnano Cadnano simplifies and enhances the process of designing three-dimensional DNA origami nanostructures. Through its user-friendly 2D and 3D interfaces it accelerates the creation of arbitrary designs. The embedded rules within cadnano paired with the finite element analysis performed by cando, provide relative certainty of the stability of the structures.

cadnano features:
Platform independent (tested in Windows, OSX and Linux)
Visual cues aid design process for stable structures
3D interface powered by Autodesk Maya*
Open architecture for plug-in creation
Free and open source (MIT license)

BIOMOD is an annual biomolecular design competition for students

Shawn is an advocate and founder of for the BIOmed project. Undergraduate teams compete to build the coolest stuff using the molecules of life. Previous winners have used DNA, RNA, and proteins as building blocks to create autonomous robots, molecular computers, and prototypes for nanoscale therapeutics. Students lead projects each summer and then travel to Harvard in early November to present their work and win awards.

BIOMOD registration is OPEN for 2014!

Organize your team
Registration is $250. Before you register, please read the criteria listed on the Requirements page. All teams are responsible for their own fund raising and travel expenses, so start early.

Shawn Douglas Google Solve for X targeted cancer therapeutics with DNA origami nanobots

Recently we had covered the Google Solve for X talk on DNA nanobot microsurgery by Ido Bachelet.

Here is the 2013 Google Solve for X talk by Shawn Douglas who led the work on the 2012 paper that was co-written by Ido Bachelet and George Church.

Shawn Douglas has his personal website here

Problem: Cancer

Solution: Nanorobots that deliver cancer drugs specifically to tumors, allowing patients to be treated by several drugs at once.

Technology: Building on the field of DNA origami, Shawn Douglas has developed a method to design and fabricate nanometer scale robots. The robots are fabricated out of DNA and have the ability to delivery cancer drugs to a specific cancer cells.

October 07, 2013

Programmable chemical controllers made from DNA

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

October 03, 2013

DNA nanotechnology opens new path to super-high-resolution molecular imaging

Researchers create blinking DNA probes that could help overcome longstanding limits of optical microscopy. It is an inexpensive and easy-to-use new microscopy method to simultaneously spot many tiny components of cells.

The DNA-based microscopy method could potentially lead to new ways of diagnosing disease by distinguishing healthy and diseased cells based on sophisticated molecular details. It could also help scientists uncover how the cell's components carry out their work inside the cell.

Wyss Institute scientists have begun programming DNA to help make specific targets in the cell blink. This leads to sharp images of cellular parts that are typically too small to see in a light microscope

September 10, 2013

DNA Glue could help reconnect injured organs or build functional human tissues

Researchers at the Wyss Institute of Biologically Inspired Engineering at Harvard University has found a way to self-assemble complex structures out of gel “bricks” smaller than a grain of salt. The new method could help solve one of the major challenges in tissue engineering: creating injectable components that self-assemble into intricately structured, biocompatible scaffolds at an injury site to help regrow human tissues.

The key to self-assembly was developing the world’s first programmable glue. The glue is made of DNA, and it directs specific bricks of a water-filled gel to adhere only to each other.

“By using DNA glue to guide gel bricks to self-assemble, we’re creating sophisticated programmable architecture,” said Peng Yin, a core faculty member at the Wyss Institute and senior co-author of the study. Yin is also an assistant professor of systems biology at Harvard Medical School (HMS). This novel self-assembly method worked for gel cubes as tiny as a piece of silt (30 microns diameter) to as large as a grain of sand (1 millimeter diameter), underscoring the method’s versatility.

Nature Communications - DNA-directed self-assembly of shape-controlled hydrogels

September 07, 2013

DNA used to Assemble a Transistor from Graphene

Stanford researchers started with a tiny platter of silicon to provide a support (substrate) for their experimental transistor. They dipped the silicon platter into a solution of DNA derived from bacteria and used a known technique to comb the DNA strands into relatively straight lines.

Next, the DNA on the platter was exposed to a copper salt solution. The chemical properties of the solution allowed the copper ions to be absorbed into the DNA.

Next the platter was heated and bathed in methane gas, which contains carbon atoms. Once again chemical forces came into play to aid in the assembly process. The heat sparked a chemical reaction that freed some of the carbon atoms in the DNA and methane. These free carbon atoms quickly joined together to form stable honeycombs of graphene.

"The loose carbon atoms stayed close to where they broke free from the DNA strands, and so they formed ribbons that followed the structure of the DNA," Yap said.

So part one of the invention involved using DNA to assemble ribbons of carbon. But the researchers also wanted to show that these carbon ribbons could perform electronic tasks. So they made transistors on the ribbons.

"We demonstrated for the first time that you can use DNA to grow narrow ribbons and then make working transistors," Sokolov said.

To the right is a honeycomb of graphene atoms. To the left is a double strand of DNA. The white spheres represent copper ions integral to the chemical assembly process. The fire represents the heat that is an essential ingredient in the technique. (Anatoliy Sokolov)

Nature Communications - Direct growth of aligned graphitic nanoribbons from a DNA template by chemical vapor deposition

August 09, 2013

Stiffening self assembled duplex and quadruplex stranded DNA nanofibers for bottom up nanofabrication

Researchers have fabricated a self-assembled nanofiber from a DNA building block that contains both duplex (two-stranded) and quadruplex (four-stranded) DNA. This work is a first step toward the creation of new structurally heterogeneous (quadruplex/duplex), yet controllable, DNA-based materials exhibiting novel properties suitable for bottom-to-top self-assembly for nanofabrication, including self-organization of both inorganic materials (nanoparticles) and molecular electronics components.

According to CNST Project Leader Veronika Szalai, this work will allow future integration with other programmable self-assembly methods such as DNA origami, as well as with other nanomaterial components such as quantum dots, to create new multi-functional biological-based nanomaterials.

Top: Schematic showing association of two duplex precursors into a quadruplex fiber building block. The duplex regions of the building block are shown in red and blue; the quadruplex region is shown in gray. Bottom: AFM image of quadruplex DNA nanofibers. These fibers can be 2 micrometers or more in length.

Nanoscale Research Letters - Synapsable quadruplex-mediated fibers

June 08, 2013

DNA synthesis that is 30 times cheaper, industrially scalable and with fewer errors will help unleash the commercialization of DNA Nanotechnology

A new method of manufacturing short, single-stranded DNA molecules can solve many of the problems associated with current production methods. The new method, which is described in the scientific periodical Nature Methods, can be of value to both DNA nanotechnology and the development of drugs consisting of DNA fragments.

"We've used enzymatic production methods to create a system that not only improves the quality of the manufactured oligonucleotides but that also makes it possible to scale up production using bacteria in order to produce large amounts of DNA copies cheaply," says co-developer Björn Högberg at the Swedish Medical Nanoscience Center, part of the Department of Neuroscience at Karolinska Institutet.

The process of bioproduction, whereby bacteria are used to copy DNA sequences, enables the manufacture of large amounts of DNA copies at a low cost. Unlike current methods of synthesising oligonucleotides, where the number of errors increases with the length of the sequence, this new method according to the developers also works well for long oligonucleotides of several hundred nitrogenous bases.

They were also able to make 378-nucleotide long oligomers at a cost 15 to 30 times less than chemically synthesize oligonucleotides

enzymatic production of ‘monoclonal stoichiometric’ single-stranded dnA oligonucleotides

March 29, 2013

DNA made into Complex 2D and 3D DNA nanostructures made from DNA wireframe meshes using new adaptable junctions

University of Arizona researcher Hao Yan has made new 2-D and 3-D objects that look like wire-frame art of spheres as well as molecular tweezers, scissors, a screw, hand fan, and even a spider web.

The twist in their 'bottom up,' molecular Lego design strategy focuses on a DNA structure called a Holliday junction.

In nature, this cross-shaped, double-stacked DNA structure is like the 4-way traffic stop of genetics – where 2 separate DNA helices temporality meet to exchange genetic information. The Holliday junction is the crossroads responsible for the diversity of life on Earth, and ensures that children are given a unique shuffling of traits from a mother and father's DNA.

In nature, the Holliday junction twists the double-stacked strands of DNA at an angle of about 60-degrees, which is perfect for swapping genes but sometimes frustrating for DNA nanotechnology scientists, because it limits the design rules of their structures.

"In principal, you can use the scaffold to connect multiple layers horizontally," [which many research teams have utilized since the development of DNA origami by Cal Tech's Paul Rothemund in 2006]. However, when you go in the vertical direction, the polarity of DNA prevents you from making multiple layers," said Yan. "What we needed to do is rotate the angle and force it to connect."

The fundamental unit in Hao Yan's new nanostructures rely on modifying a 4-arm DNA junction. The relaxed DNA geometry found in a 4-arm junction (B) can be rotated 150 degrees clockwise or 30 degrees counterclockwise (C) to form the right angles needed to make a DNA Gridiron (D and E).
Photo by: Biodesign Institute

Science - DNA Gridiron Nanostructures Based on Four-Arm Junctions

March 20, 2013

DNA Nano-Assembly can be scaled up and also assemble inorganic materials

An 18 page presentation on Nano-Assembly using DNA bricks by Peng Yin of Harvard.

This is a plan for scaling up DNA Brick Nanoassembly and to enable the use of DNA nanotechnology as scaffolding for other inorganic molecular nanatechnology.

DNA can already be assembled into many structures as shown below

Scaling up DNA Bricks
Hierarchical assembly
NanoAssembler: iterative, solid phase synthesis of geometry

DNA can become scaffolds for functional materials
Fluorescent barcodes for multiplexed imaging
DNA “nanorobot” for targeted delivery
Chiral gold arrays for “Carving light"

March 04, 2013

DNA 3D Nand Gate Bricks Would Be Able to Make a Computer with 1 million times the transistors of Intel Itanium Poulson Computers

Harvard researchers have used single strand DNA, to self assemble custom designed nano scale structures. Each of the bricks shown to the left is, 25-nanometers on a side, they are composed of ~1,000 voxels (I think it is 500 DNA strand, 2 voxels per strand) unique single strands of DNA, each with 32 nucleotides. Each strand is like a jigsaw puzzle piece and can only bind in one location. This is due to the fact that nucleotides only bind to their opposites, A to T and G to C. These DNA strands can be designed to self assemble into pretty much any shape, as shown in the image.

David Fuchs at Hephastus Project outlines what kind of computing would be possible with 25 nanometer 3D Nand bricks.

A one inch cube could hold 1,000,000,000,000,000,000 of these 25 nm bricks.

Using two simple techniques, you can build much larger structures out of smaller ones. The first technique is to create binding sites, on each of the six sides of the brick. The second technique is to create a spacer-binder with matching but opposite nucleotides to bind to.

NOTE - Limiting factors.
* cost to produce this much DNA is still out of reach
It costs $2 billion to synthesize the billions of base pairs for the human genome. There are some approaches which could lower the cost by 10,000 to 100,000 times but that is still $20,000 for a human genome. Even if short sequence DNA brick synthesis is a lot cheaper in massively parallel production that has to be very cheap synthesis of 260 billion billion 25 nanometer bricks.

* connecting it and making the structure and logic for useful work and providing the skeleton for massive number of bricks seems to pretty much need full blown molecular nanotechnology.

* there is also the heat management issues

December 13, 2012

Time for DNA Manufacturing reduced from weeks to minutes and process for validation of the manufactured DNA structures enabled

Eurekalert - Two major barriers to the advancement of DNA nanotechnology beyond the research lab have been knocked down. This emerging technology employs DNA as a programmable building material for self-assembled, nanometer-scale structures. Many practical applications have been envisioned, and researchers recently demonstrated a synthetic membrane channel made from DNA. Until now, however, design processes were hobbled by a lack of structural feedback. Assembly was slow and often of poor quality. Now researchers led by Prof. Hendrik Dietz of the Technische Universitaet Muenchen (TUM) have removed these obstacles.

One barrier holding the field back was an unproven assumption. Researchers were able to design a wide variety of discrete objects and specify exactly how DNA strands should zip together and fold into the desired shapes. They could show that the resulting nanostructures closely matched the designs. Still lacking, though, was the validation of the assumed subnanometer-scale precise positional control. This has been confirmed for the first time through analysis of a test object designed specifically for the purpose. A technical breakthrough based on advances in fundamental understanding, this demonstration has provided a crucial reality check for DNA nanotechnology.

In a separate set of experiments, the researchers discovered that the time it takes to make a batch of complex DNA-based objects can be cut from a week to a matter of minutes, and that the yield can be nearly 100%. They showed for the first time that at a constant temperature, hundreds of DNA strands can fold cooperatively to form an object — correctly, as designed — within minutes. Surprisingly, they say, the process is similar to protein folding, despite significant chemical and structural differences. "Seeing this combination of rapid folding and high yield," Dietz says, "we have a stronger sense than ever that DNA nanotechnology could lead to a new kind of manufacturing, with a commercial, even industrial future." And there are immediate benefits, he adds: "Now we don't have to wait a week for feedback on an experimental design, and multi-step assembly processes have suddenly become so much more practical."

Caption: This 3-D print shows a DNA-based structure designed to test a critical assumption -- that such objects could be realized, as designed, with subnanometer precision. This object is a relatively large, three-dimensional DNA-based structure, asymmetrical to help determine the orientation, and incorporating distinctive design motifs. Subnanometer-resolution imaging with low-temperature electron microscopy enabled researchers to map the object -- which comprises more than 460,000 atoms -- with subnanometer-scale detail. Credit: Dietz Lab, TU Muenchen

Three research papers detail the work

Science - Rapid Folding of DNA into Nanoscale Shapes at Constant Temperature

November 29, 2012

Researchers Create Versatile 3D Nanostructures Using DNA "Bricks"

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have created more than 100 three-dimensional (3D) nanostructures using DNA building blocks that function like Lego® bricks -- a major advance from the two-dimensional (2D) structures the same team built a few months ago.

In effect, the advance means researchers just went from being able to build a flat wall of Legos®, to building a house. The new method, featured as a cover research article in the 30 November issue of Science, is the next step toward using DNA nanotechnologies for more sophisticated applications than ever possible before, such as "smart" medical devices that target drugs selectively to disease sites, programmable imaging probes, templates for precisely arranging inorganic materials in the manufacturing of next generation computer circuits, and more.

The nanofabrication technique, called "DNA-brick self-assembly," uses short, synthetic strands of DNA that work like interlocking Lego® bricks. It capitalizes on the ability to program DNA to form into predesigned shapes thanks to the underlying "recipe" of DNA base pairs: A (adenosine) only binds to T (thymine) and C (cytosine) only binds to G (guanine).

Computer-generated 3D models (left) and corresponding 2D projection microscopy images (right) of nanostructures self-assembled from synthetic DNA strands called DNA bricks. A master DNA brick collection defines a 25-nanometer cubic "molecular canvas" with 1000 voxels. By selecting subsets of bricks from this canvas, Ke et al. constructed a panel of 102 distinct shapes exhibiting sophisticated surface features as well as intricate interior cavities and tunnels. These nanostructures may enable diverse applications ranging from medicine to nanobiotechnology and electronics. [Image Credit: Yonggang Ke, Wyss Institute, Harvard University.]

September 11, 2012

Osamu Tabata – DNA origami for assembling nanomachines - Cells, receptor proteins, enzymes and DNA have outstanding properties. The question is, can they also be used as building blocks in computer processors, sensor systems and other micromachines in next generation microelectronics? In cooperation with his research group at the University of Kyoto and his partners in Freiburg, Prof. Dr. Osamu Tabata, microengineer and External Senior Fellow at the Freiburg Institute for Advanced Studies (FRIAS) is working on the development of a new generation of micromachines based on folded DNA molecules that is smaller, more intelligent and better than the previous generation.

Prof. Osamu Tabata, External Senior Fellow at the School of Soft Matter Research at the Freiburg Institute for Advanced Studies (FRIAS) is a pioneer of MEMS.

The future of the art of engineering

Biological elements such as cells, receptor proteins, enzymes and DNA have amazing properties: they can recognize individual molecules, conduct light energy and catalyze chemical reactions, to name just a few properties. “Can they be used as components of next-generation microelectronics systems such as computer processors, sensor systems, MEMS and other micromachines?” asks Tabata, who is a professor in the Department of Microengineering Sciences at Kyoto University in Japan. “And how can biological elements be combined with microelectronic systems?” Tabata is certain that bionanotechnology will have a huge impact on engineering in the future. Currently focused on the basic aspects, it is such visions that have driven his research from the very beginning back in the day when the term “microelectromechanical systems” had not yet been coined.

The DNA origami method enables the researchers to fold DNA molecules into complicated scaffolds. (© Prof. Dr. Osamu Tabata)