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).
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22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
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