More than 15 years ago scientists discovered a way to stop a particular gene in its tracks. The Nobel Prize-winning finding holds tantalizing promise for medical science, but so far it has been difficult to apply the technique, known as RNA interference, in living cells.
Now scientists at the University of Washington in Seattle and Emory University in Atlanta have succeeded in using nanotechnology known as quantum dots to address this problem. Their technique is 10 to 20 times more effective than existing methods for injecting the gene-silencing tools, known as siRNA, into cells.
"We believe this is going to make a very important impact to the field of siRNA delivery," said Xiaohu Gao, a UW assistant professor of bioengineering and co-author of a study published online this week in the Journal of the American Chemical Society.
"This work helps to overcome the longstanding barrier in the siRNA field: How to achieve high silencing efficiency with low toxicity,” said co-author Shuming Nie, a professor in the Wallace H. Coulter Department of Biomedical Engineering, jointly affiliated with the Georgia Institute of Technology and Emory University.
Other co-authors are Maksym Yezhelyev and Ruth O'Regan at Emory and Lifeng Qi at the UW.
Short pieces of RNA, the working copy of DNA, can disable production of a protein by silencing, or deactivating, a stretch of genetic code. Research laboratories regularly use the technique to figure out what a particular gene does. In the body, RNA interference could be used to treat conditions ranging from breast cancer to deteriorating eyesight.
The recent experiments used quantum dots, fluorescent balls of semiconductor material just six nanometers across (lining up 9,000 dots end to end would equal the width of a human hair). Quantum dots' unique optical properties cause them to emit light of different colors depending on their size. The dots are being developed for cellular imaging, solar cells and light-emitting diodes.
This paper describes one of the first applications of quantum dots to drug delivery.
Each quantum dot was surrounded by a proton sponge that carried a positive charge. Without any quantum dots attached, the siRNA's negative charge would prevent it from penetrating a cell's wall. With the quantum-dot chaperone, the more weakly charged siRNA complex crosses the cellular wall, escapes from the endosome (a fatty bubble that surrounds incoming material) and accumulates in the cellular fluid, where it can do its work disrupting protein manufacture.
Key to the newly published approach is that researchers can adjust the chemical makeup of the quantum dot's proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the siRNA.
Quantum dots were dramatically better than existing techniques at stopping gene activity. In experiments, a cell's production of a test protein dropped to 2 percent when siRNA was delivered with quantum dots. By contrast, the test protein was produced at 13 percent to 51 percent of normal levels when the siRNA was delivered with one of three commercial reagents, or reaction-causing substances, now commonly used in laboratories.
Central to the finding is that fluorescent quantum dots allow scientists to watch the siRNA's movements. Previous siRNA trackers gave off light for less than a minute, while quantum dots, developed for imaging, emit light for hours at a time. In the experiments the authors were able to watch the process for many hours to track the gene-silencer's path.
The new approach is also five to 10 times less toxic to the cell than existing chemicals, meaning the quantum dot chaperones are less likely to harm cells. The ideal delivery vehicle would have no effect; the only biological change would be siRNA blocking cells' production of an unwanted protein.
The exact reason that the quantum dots were more effective than previous techniques is, however, still a mystery.
"We believe the improvement is caused by the endosome escape, and the ability of the quantum dots to separate from the siRNA," Gao said.Quantum dots are not yet approved for use in humans. The authors are now transferring their techniques to particles of iron oxide, several types of which have been approved by the Food and Drug Administration for use in humans.
They are also working to target cancer cells by attaching to specific markers on the cells' surface.
“Looking forward, this work will have important implications in in-vivo siRNA therapeutics, which will require the use of nontoxic iron oxide and biodegradable polymeric carriers rather than quantum dots,” Nie said.
The research was funded by grants from the National Institutes of Health, the National Science Foundation and the Georgia Cancer Coalition.
For more information, contact Gao at (206) 543-6562 or firstname.lastname@example.org and Nie at (404) 712-8595, (404) 727-0391 or email@example.com.
Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences