Designing Synthetic Virus Particles for Gene Therapy
Researchers from Wageningen UR, together with colleagues from the University of Leiden, Eindhoven University of Technology and Radboud University Nijmegen, have successfully developed an artificial virus. This virus can be More info
used for the delivery of future generations of pharmaceuticals by 'packaging' them and delivering them to diseased cells. Dr. Daniela Kraft of Leiden University and prof. dr. ir. Paul van der Schoot (TU/e) were responsible for the theoretical underpinning that led to the design of the synthetic protein. The scientists present their findings in an article published in Nature Nanotechnology on August 24th 2014.
Bringing large biomolecules such as DNA or RNA to a desired location poses a great challenge for new generations of pharmaceuticals. DNA for example cannot by itself enter cells, and is quickly degraded by enzymes.
Natural viruses are highly effective in transferring DNA or RNA into cells. They do this by encapsulating and protecting their genetic material (RNA or DNA) with proteins. Natural viruses therefore bear great potential for therapies, but a health risk remains, and scientists are therefore looking for harmless alternatives.
The inspiration for the research published in Nature Nanotechnology came from a theoretical model that describes the assembly of a natural virus, tobacco mosaic virus. Dr. Daniela Kraft of Leiden University and prof. dr. ir. Paul van der Schoot of TU Eindhoven recently developed this model together with prof. dr. Willem Kegel of Utrecht University. They investigated, how the natural virus achieves full protection of its genetic material. The crucial element for successful encapsulation is cooperativity, which ensures that the proteins help each other to bind to the genetic material.
The design of the novel synthetic protein, which the scientists now presented, incorporates a similar cooperative domain based on silk. The synthetic protein consists of natural proteins such as collagen and spontaneously encapsulates DNA to form artificial viruses. Despite its simplicity, the synthetic virus resembles in many ways its natural counterpart. For example, its assembly dynamics can be described with the theoretical model that inspired the design, and the protein coat efficiently protects the DNA and transfers it to cells.
The synthetic virus particles may be employed to bring new generations of medications such as DNA into diseased cells in a safe way, and thus be particularly useful for gene therapy.
Design and self-assembly of simple coat proteins for artificial viruses,
Hernandez-Garcia et al., Nature Nanotechnology, doi:10.1038/nnano.2014.169
(published online 24 August 2014)
Sanli Faez reports on: Topologically protected photons avoid Anderson localization.
Waves can propagate through a large ensemble of random obstacles by diffusion. This general mechanism allows light (electromagnetic waves) to travel through thick clouds and facilitate electrons (Schrödinger waves) to More info
conduct a current through very large (relative to the free propagation length of electrons) disordered lattices such as metallic wires. Waves are also subject to interference, as can be demonstrated by the famous Young’s double-slit experiment. The interplay of disorder and interference can however bring wave diffusion to a complete halt. This remarkable phenomenon, first envisaged by Philip Anderson in 1958, is known as Anderson localization and has been investigated, from various perspectives, in a wide range of systems that exhibit wave or quantum transport. This interference effect is usually more prominent in low-dimensional systems where multiply-scattered paths are more likely to go in circles and hence exhibit stronger interference.
There are however a few systems in which transport is partly immune to Anderson localization. The most notable example is the quantum Hall effect, in which electrons, under the influence of a large magnetic field can execute tiny cyclonic orbits for which the two propagation directions cannot mix by scattering and thereafter localization is suppressed. In some materials, called topological insulators, no external magnetic field is needed since the necessary field is supplied by spin-orbit interactions that is, the coupling between the orbital motion of electrons and their spins. In these materials the conduction regime is called topological as the material is conductive only around the edge while it is an insulator in the interior. What makes topological states even more interesting is that the quantum information in the state of the electrons is also better protected from disturbance of the environment than in normal electronic states.
These intriguing transport properties have inspired physicists to envisage photonic equivalents. Light waves, however, do not usually feel magnetic fields, and if they do it is very weak. Inspired by discoveries in condensed-matter physics, researchers have sought alternative ways to realize topological protection of light transport.
One of the recent photonic devices, originally suggested by Hafezi and his collaborators at the University of Maryland, USA, uses a special arrangement of ring resonators to emulate a quantum spin Hall system. The loops in the array are of two kinds: 1- resonator loops designed to exactly accommodate light at a certain frequency and 2-anti-resonant link loops, to pass the light between neighboring loops of the first kind. The equivalent of a magnetic field in this device is supplied by a subtle phase shift imposed on the light as it circulates around the loops. Light that circulates around one unit cell of the loop array will undergo a pre-determined phase change. That is, the light signal, in coming around the unit cell, re-arrives where it started advanced or retarded just a bit from its original condition. Just this amount of change imparts the topological robustness to the global transmission of the light in the array.
One of the advantages of optical measurements is their direct access to the phase information of the transmission channels. In their recent investigation the Maryland group and their collaborator at Leiden University have used this phase information to quantitatively demonstrate the topological robustness against disorder in their devices. The experimental measurements performed on numerous array samples, reveal that for light taking the bulk (interior) route in the array, the delay and transmission of light can vary a lot, whereas for light making the edge route, the amount of energy loss is regularly less and the time delay for signals more consistent. Robustness and consistency are vital if one needs a practical photonic device, for example for processing quantum information.
Their research is published in Physical Review Letters, selected as Editors' Suggestion, and accompanied by a viewpoint in Physics. One of the referees has praised this work by stating that “this paper brings together the fields of topological material and the statistics of disordered media for the first time.”
About the image: Light enters a two-dimensional ring-resonator array from the lower left and exits at the lower right. Light that follows the edge of the array (blue) does not suffer energy loss and exits after a consistent amount of delay. Light that travels into the interior of the array (green) suffers energy loss.
Viewpoint: Light Avoids Anderson Localization, Alexander Khanikaev and Azriel Genack, Physics 7, 87
FOM Institute AMOLF is launching a new line of research in designer matter, aimed at
the design of new forms of functional matter. Professor Martin van Hecke (Leiden
University) will lead a More info
new research group at AMOLF, with effect from 1 September 2014,
in the area of mechanical metamaterials. Together with Van Hecke, AMOLF will further
expand the broad line of research into designer matter over the next few years. Van Hecke
will continue to spend half of his time at Leiden University.
Congratulations to Dirk Bouwmeester who has received the NWO Spinoza Prize 2014 from the Netherlands Organisation for Scientific Research. This was announced today by Jos Engelen, chair of the Netherlands More info
Organisation for Scientific Research (NWO). The NWO Spinoza Prize is the highest award in Dutch science. This autumn each of the laureates will receive 2.5 million euros to spend on scientific research.
S. Mittal, J. Fan, S. Faez, A. Migdall, J. M. Taylor, and M. Hafezi (2014) Topologically Robust Transport of Photons in a Synthetic Gauge Field., Phys.Rev.Lett., 113, 087403. [Abstract][DOI][pdf]
Hedde van Hoorn, Rolf Harkes, Ewa M. Spiesz, Cornelis Storm, Danny van Noort, Benoit Ladoux, and Thomas Schmidt (2014) The Nanoscale Architecture of Force-Bearing Focal Adhesions., Nano Lett., 14, 4257–4262. [Abstract][DOI][pdf]
5 Sept, 16:00:00,
Van der Waals Colloquium Prof. Manabu Kiguchi: Single molecular dynamics using the Surface enhanced Raman scattering.
12 Sept, 16:00:00,
Van der Waals Colloquium Daniel Bonn (UvA):
25 Sept, 12:30:00, C.J. Gorterzaal
Scientific Council - Wetenschappelijke Raad (WeRa) Meeting for staff members only