A recent article in Nature documents how a Danish multidisciplinary team of researchers created 3D nano-sized boxes out of single long strands of DNA. The researchers were then able to lock or unlock these boxes in response to ‘keys’ made from short external strands of DNA. The ability to regulate access to the boxes according to various forms of keys has opened a range of their possible applications from sensors to accurate drug delivery systems.
DNA ‘origami’
The 3D DNA boxes were formed via a technique known as DNA ‘origami’. It utilises the characteristic of complementary DNA to self-recognise and ‘pair up’ together. In DNA ‘origami’, short segments of complementary DNA (oligonucleotides) are used as ‘staples’ to join the target areas of DNA together, and fold the DNA into the desired shape. This process is aided by using a recently developed design software program that when given the desired shape, selects and outputs the some 250 oligonucleotides that will assemble it.
Nevertheless, research into this field had been previously limited to 2D structures, and to open ended tubes. The Danish team developed the technique further to create their six faced box and lid. In their case the researchers used a circular strand of DNA from the bacteriophage M13. After using the program to calculate the appropriate oglionucleotide combination, they mixed the 220 ‘staples’ with the bacteriophage DNA and heated them. The boxes then self-assembled by first creating the walls and then joining them together. The researchers were able to confirm this shape through cryogenic transmission electron microscopy and small angle X ray scattering.
‘Lock’ and ‘Key’ mechanism
What makes this research truly exciting and potentially useful, however, was the discovery that a ‘lock’ sequence of DNA could be attached via an oglionucleotide that joined the lid and the box shut and which contained a ‘sticky-end’ where a supplied segment of ‘key’ DNA could attach and ‘unlock’ the box by strand displacement. Furthermore, a number of ‘locks’ with varying keys could be attached for further complexity. The state of the lid was detected by fluorescent activity (closed – red, open – green). This programmability and control of the inner compartment of the box therefore is determined by the presence of the external ‘key’ DNA stimuli.
This control via an external stimuli means that these boxes have a range of possible and interesting applications. The foremost of these is that they could be used for controlled release, as in the case of drug delivery. Tiny molecules of drugs could be released in response to a specific external stimuli. Alternatively, the boxes could be used as a sensor for something that induces the box to change state.
DIY DNA:
The design software program used by the research team can be found and download online http://www.cdna.dk/origami/ .
REFERENCES:
Andersen, E. S. et al. Nature 459, 73–76 (2009).
