Among the most powerful molecular biology techniques to emerge in recent years is RNA interference, in which small interfering RNA (siRNA) molecules are used to target specific genes to reduce their expression in living organisms. siRNAs have delivered considerable precision and efficiency in modulating gene expression in the laboratory, and many see considerable promise in clinical applications of this technology, although serious technical roadblocks remain to be overcome.
Chief among these is finding a safe and effective means for siRNA delivery. Simple injection of siRNAs is not an option, as RNA is rapidly degraded in the body, and so more complicated strategies are required—each with its own issues.
“Virus vectors that proliferate in vivo are potentially risky … vector systems can not be controlled in cells, and the dose of RNA is very important for clinical RNA interference,” explains Hiroshi Abe, a research scientist in Yoshihiro Ito’s laboratory at the RIKEN Discovery Research Institute in Wako. “If excess RNA is administered, cells respond to foreign body using the immune system.” Another possibility involves the use of chemically modified RNAs that can survive longer within the body, but Abe points out that this stability comes at the cost of reduced efficacy at gene silencing.
Since RNA-degrading enzymes typically start by chewing at loose RNA ends, Ito’s team has taken an innovative approach to deliver natural RNA effectively—they circularized their siRNAs (Fig. 1), designing molecules that self-assembled into stable ‘dumbbell’ shapes1. Since siRNAs begin as double-stranded precursors that must be processed by the enzyme Dicer before they can be effective, a key concern of the team was ensuring that their dumbbell constructs were not just stable, but also capable of being processed by Dicer. The dumbbells performed well on both counts; they outlasted linear siRNA molecules in human serum, and also surpassed linear molecules at triggering specific inhibition of targeted genes when injected into cultured human fibroblast cells.
Encouraged by these initial findings, Ito, Abe and colleagues are now looking into strategies to further enhance the effectiveness of their constructs. These extra-stable dumbbells are also more resistant to processing by Dicer, which reduces their inhibitory capabilities, and Abe indicates that optimizing the dumbbell’s loop structure is now a top priority. In parallel, the researchers are also exploring new methods for siRNA synthesis that could make it easier to scale up production for future studies.
1. Abe, N., Abe, H. & Ito, Y. Dumbbell-shaped nanocircular RNAs for RNA interference. Journal of the American Chemical Society 129, 15108–15109 (2007).
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Materials Sciences
18.07.2018 | Life Sciences
18.07.2018 | Health and Medicine