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).
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences