Cool thing- a DNA nanobox
EJ
DNA box with a controllable lid.
"By exploiting the unique structural motifs and self-recognition
properties of DNA, it is possible to generate self-assembled DNA
nanostructures of specific shapes. Here, a previously described DNA
'origami' method has been extended into three dimensions to create an
addressable DNA box on the nanometre scale that can be opened by an
externally supplied DNA key'. "
"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' approach. 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"
http://www.nature.com/nature/journal/v459/n7243/abs/nature07971.html?lang=en
Bryan Bishop
> "By exploiting the unique structural motifs and self-recognition
> properties of DNA, it is possible to generate self-assembled DNA
> nanostructures of specific shapes. Here, a previously described DNA
> 'origami' method has been extended into three dimensions to create an
> addressable DNA box on the nanometre scale that can be opened by an
> externally supplied DNA key'. "
Self-assembly of a nanoscale DNA box with a controllable lid.
http://heybryan.org/books/papers/Self-assembly%20of%20a%20nanoscale%20DNA%20box%20with%20a%20controllable%20lid.pdf
That sounds neat. What it made me think of is the work that has been
done on light-controlled gene silencing or inhibition of specific
oligonucleotide strands via coupling to an azobenzene (IIRC).
Regulating gene expression with light-activated oligonucleotides
http://heybryan.org/books/papers/Regulating%20gene%20expression%20with%20light-activated%20oligonucleotides.pdf
Light-controlled gene silencing in zebrafish embryos
http://heybryan.org/books/papers/Light-controlled%20gene%20silencing%20in%20zebrafish%20embryos.pdf
Light-activation of gene function in mammalian cells via ribozymes
http://heybryan.org/books/papers/Light-activation%20of%20gene%20function%20in%20mammalian%20cells%20via%20ribozymes.pdf
Gene silencing in mammalian cells with light-activated antisense agents
http://heybryan.org/books/papers/Gene%20silencing%20in%20mammalian%20cells%20with%20light-activated%20antisense%20agents.pdf
I have not done any analysis, so the following is purely imagination
at play, but it would be really interesting to see azobenzene
molecules responding to different wavelengths of light, so that you
could have more than one or two different DNA 'keys' in your
DNA-origami-box-soup. By changing the frequency of light (or simply
using different wavelength lasers or maybe LEDs with different plastic
filters), you could control which boxes open and close. Through the
sequencing of different boxes opening and closing, you get finer
control over molecular mixing and reactions of (I'm guessing)
femto-liter volume fluids. So, instead of laboriously adding different
DNA strands to the mix, they are always present, and it would be an
issue of light rather than mechanical addition of chemical compounds-
but now the trick is figuring out what to do with this sort of
specificity over nanocargoes. Binding them to some antibody or
biotinylating them to some streptavidin on a surface of nanowells, or
incorporating them into a water-in-emulsion system, might prove
interesting for in vitro compartmentalization experiments (directed
evolution). It's odd, I don't know how to quite think about the
options that this would allow. It's like 'discrete digital control
over molecular reactions in bulk but with addressable specifity and
possibly some cool stuff involving lasers', but 'discrete digital
control over molecular reactions' does not describe what it's like to
turn on and off different compartments. Oh well. I'll have to think
about this some more. Thanks for the neat paper.
Bryan Bishop
Someone beat me to it.
A Yoctoliter-Scale DNA Reactor for Small-Molecule Evolution
Margit Haahr Hansen, Peter Blakskjær, Lars Kolster Petersen, Tara
Heitner Hansen, Jonas Westergaard Højfeldt, Kurt Vesterager Gothelf,
and Nils Jakob Vest Hansen
The center of DNA three-way junctions, constituting a yoctoliter
(10-24 L) volume, is applied as an efficient reactor to create
DNA-encoded libraries of chemical products. Amino acids and short
peptides are linked to oligonucleotides via cleavable and noncleavable
linkers. The oligonucleotide sequences contain two universal
assembling domains at the center and a distal codon sequence specific
for the attached building block. Stepwise self-assembly and chemical
reactions of these conjugates in a combinatorial fashion create a
library of pentapeptides in DNA three-way junctions in a single
reaction vessel. We demonstrate the formation of an evenly distributed
library of 100 peptides. Each library member contains a short
synthetic peptide attached to a unique genetic code creating the
necessary “genotype-phenotype” linkage essential to the process of in
vitro molecular evolution. Selective enrichment of the
[Leu]-enkephalin peptide from an original frequency of 1 in 10 million
in a model library to a final frequency of 1.7% in only two rounds of
affinity selection is described and demonstrates successful molecular
evolution for a non-natural system