Nucleic acid structure and dynamics
Structural DNA nanotechnology is an emerging field that seeks to create exquisitely defined nanoscale architectures via the self-assembly of a set of carefully chosen DNA sequences. With a diameter of 2 nm and a helical periodicity of 3.5 nm, the DNA double helix is inherently a nanoscale object. The specificity and predictable affinities of Watson-Crick base pairing affords a hierarchy of molecular glues between given rods at defined locations that makes DNA an ideal nanoscale construction material. DNA nanodevices could either be rigid scaffolds in 1D, 2D or 3D that function as molecular breadboards. They could also function as switches or transducers, undergoing controlled nanomechanical motion, by exhibiting a conformational change in response to a stimulus. We create such DNA-based nanodevices for applications as high-performance 'custom' biosensors that intercept biochemical signals, thereby interrogating and reporting on cellular processes.
Krishnan, Y., Simmel. F. C. Nucleic Acid Based Molecular Devices. Angew. Chem. Int. Ed., 2011, 50, 3124 – 3156
DNA nanomachines are nothing but molecular switches. These are artificially designed assemblies that switch between defined conformations in response to an external cue. One of the devices made by our lab is the I-switch, which is a DNA nanomachine that undergoes a conformational change triggered by protons. Though it has proved possible to create DNA machines and rudimentary walkers, the first demonstration that they could function inside living systems came from our group. We showed that one could effectively map spatiotemporal pH changes associated with endosomal maturation both in living cells as well as within cells present in a living organism. Recently, we deployed the first nucleic acid based chloride sensor inside living cells and measured chloride concentrations in endocytic pathway. We are making quantitative reporters of second messenger concentrations within living systems that will eventually position DNA nanodevices as exciting and powerful tools for intracellular traffic.
Modi, S., Swetha, M. G., Goswami, D., Gupta, G. D., Mayor, S., Krishnan, Y.* A DNA nanomachine that maps spatial and temporal pH changes in living cells. Nature Nanotechnology, 2009, 4, 325-330
DNA Icosahedra for encapsulation and delivery
3D DNA polyhedra could have applications in drug delivery given that they have hollow internal cavities in which functional macromolecules may be housed and targeted. To this end we have shown that DNA can be used to make complex polyhedra such as an icosahedron, using a novel, modular assembly based approach. The power of this approach is that it allows the efficient encapsulation of other nanoscale entities in high yields. Many peptide based drugs cannot be delivered efficiently to their target due to degradation. Thus encapsulating them in non-leaky, programmable capsules such as DNA polyhedra might solve this problem.
Bhatia, D., Mehtab, S., Krishnan, R., Indi, S.S., Basu, A., Krishnan, Y.* Icosahedral DNA nanocapsules via modular assembly. Angew. Chem. Int. Ed., 2009, 48, 4134 – 4137
Banerjee, A., Bhatia, D., Saminathan, A., Chakraborty, S., Kar, S., Krishnan, Y.* Controlled release of encapsulated cargo from a DNA Icosahedron using a chemical trigger. Angew. Chem. Int. Ed. 2013, 52, 6854-6857