For the past decade, scientists have been pursuing cancer treatments based on RNA interference — a phenomenon that offers a way to shut off malfunctioning genes with short snippets of RNA. However, one huge challenge remains: finding a way to efficiently deliver the RNA.
Most of the time, short interfering RNA (siRNA) — the type used for RNA interference — is quickly broken down inside the body by enzymes that defend against infection by RNA viruses.
"It's been a real struggle to try to design a delivery system that allows us to administer siRNA, especially if you want to target it to a specific part of the body," says Paula Hammond, the David H. Koch Professor in Engineering at MIT.
Hammond and her colleagues have now come up with a novel delivery vehicle in which RNA is packed into microspheres so dense that they withstand degradation until they reach their destinations. The new system, described Feb. 26 in the journal Nature Materials, knocks down expression of specific genes as effectively as existing delivery methods, but with a much smaller dose of particles.
Such particles could offer a new way to treat not only cancer, but also any other chronic disease caused by a "misbehaving gene," says Hammond, who is also a member of MIT's David H. Koch Institute for Integrative Cancer Research. "RNA interference holds a huge amount of promise for a number of disorders, one of which is cancer, but also neurological disorders and immune disorders," she says.
Lead author of the paper is Jong Bum Lee, a former postdoc in Hammond's lab. Postdoc Jinkee Hong, Daniel Bonner PhD '12 and Zhiyong Poon PhD '11 are also authors of the paper.
RNA interference is a naturally occurring process, discovered in 1998, that allows cells to fine-tune their genetic expression. Genetic information is normally carried from DNA in the nucleus to ribosomes, cellular structures where proteins are made. siRNA binds to the messenger RNA that carries this genetic information, destroying instructions before they reach the ribosome.
Scientists are working on many ways to artificially replicate this process to target specific genes, including packaging siRNA into nanoparticles made of lipids or inorganic materials such as gold. Though many of those have shown some success, one drawback is that it's difficult to load large amounts of siRNA onto those carriers, because the short strands do not pack tightly.
To overcome this, Hammond's team decided to package the RNA as one long strand that would fold into a tiny, compact sphere. The researchers used an RNA synthesis method known as rolling circle transcription to produce extremely long strands of RNA made up of a repeating sequence of 21 nucleotides. Those segments are separated by a shorter stretch that is recognized by the enzyme Dicer, which chops RNA wherever it encounters that sequence.
As the RNA strand is synthesized, it folds into sheets that then self-assemble into a very dense, sponge-like sphere. Up to half a million copies of the same RNA sequence can be packed into a sphere with a diameter of just two microns. Once the spheres form, the researchers wrap them in a layer of positively charged polymer, which induces the spheres to pack even more tightly (down to a 200-nanometer diameter) and also helps them to enter cells.
After the spheres enter a cell, the Dicer enzyme chops the RNA at specific locations, releasing the 21-nucleotide siRNA sequences.
In the Nature Materials paper, the researchers tested their spheres by programming them to deliver RNA sequences that shut off a gene that causes tumor cells to glow in mice. They found that they could achieve the same level of gene knockdown as conventional nanoparticle delivery, but with about one-thousandth as many particles.
The microsponges accumulate at tumor sites through a phenomenon often used to deliver nanoparticles: The blood vessels surrounding tumors are "leaky," meaning that they have tiny pores through which very small particles can squeeze.
In future studies, the researchers plan to design microspheres coated with polymers that specifically target tumor cells or other diseased cells. They are also working on spheres that carry DNA, for potential use in gene therapy.
Written by Anne Trafton, MIT News
Kimberly Allen | EurekAlert!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine