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Wednesday, May 6, 2009

DNA Boxes Could Deliver Drugs

Chemistry World is reporting that Danish researchers have made a nano-sized box out of DNA that can be locked or opened in response to 'keys' made from short strands of DNA. By changing the nature or number of these keys, it should be possible to use the boxes as sensors, drug delivery systems or even molecular computers.

To make the box shape, the team took a long, circular single strand of DNA from a virus that infects bacteria called bacteriophage M13. This M13 sequence is a cheap source of single-stranded DNA and is convenient size for building with. To turn this ring of DNA into a box, the team used a computer to work out exactly the right combination of short strands of complementary DNA which could 'staple' the appropriate areas of the ring together to get the desired box shape. When they mixed the M13 strand with the 220 short 'staple strands' and heated them up for an hour, the boxes neatly self-assembled.

Kjems reveals that the group have already had some success with putting cargo inside the boxes, including enzymes and quantum dots. 'It's quite big (about 30nm) inside - it could fit virus particles or quite big enzymes and other macromolecules.' In terms of applications, Kjems can foresee three main purposes for the box: 'One is as a calculator or logic gate; the second is for controlled release, for example of drugs, in response to external stimuli; and the last is as a sensor - where the thing you are sensing causes the box to open or close and give a readout.'

The DNA origami technique is quite straightforward, Mao comments, so could be applied to all sorts of similar structures. The fact that the box can be easily opened and closed also makes it ideal for moving guest molecules around. 'I'm really looking forward to seeing what the group do next,' he adds.

MIT Technology Review also has coverage.

Deoxyribose sugar cubes: Because complementary regions of DNA like to pair up, researchers were able to design a long strand of DNA that, combined with many tiny DNA staples, would automatically assemble itself into a nano-sized box. This technique is known as DNA origami. Here, the boxes were imaged using cryo-electron tomography to confirm their cubelike structures and hollow interior.
Credit: : Ebbe S. Andersen, Aarhus University

21 pages of supplemental information from the Journal Nature article.

The abstract in the journal Nature. [Nature 459, 73-76 (7 May 2009) | doi:10.1038/nature07971; Received 9 November 2008; Accepted 6 March 2009]
Self-assembly of a nanoscale DNA box with a controllable lid

The unique structural motifs and self-recognition properties of DNA can be exploited to generate self-assembling DNA nanostructures of specific shapes using a 'bottom-up' approach1. Several assembly strategies have been developed for building complex three-dimensional (3D) DNA nanostructures. Recently, the DNA 'origami' method was used to build two-dimensional addressable DNA structures of arbitrary shape that can be used as platforms to arrange nanomaterials with high precision and specificity. A long-term goal of this field has been to construct fully addressable 3D DNA nanostructures. Here we extend the DNA origami method into three dimensions by creating an addressable DNA box 42 36 36 nm3 in size that can be opened in the presence of externally supplied DNA 'keys'. We thoroughly characterize the structure of this DNA box using cryogenic transmission electron microscopy, small-angle X-ray scattering and atomic force microscopy, and use fluorescence resonance energy transfer to optically monitor the opening of the lid. Controlled access to the interior compartment of this DNA nanocontainer could yield several interesting applications, for example as a logic sensor for multiple-sequence signals or for the controlled release of nanocargos.


The DNA origami design software program with documentation and tutorials is
available here:


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Manta Instruments said...

In any case, the purpose behind controlling the drug delivery is to achieve more effective therapies while eliminating the potential for both under- and overdosing. Nanoparticle Characterization Techniques