Peixuan Guo, PhD, Dane and Mary Louise Miller Endowed Chair and professor of biomedical engineering, and his colleagues in UC's College of Engineering and Applied Sciences report the construction of a thermodynamically stable RNA nanoparticle online in the journal Nature Nanotechnology.
The nanoparticle, constructed from a three-way junction (3WJ) motif of packaging RNA (pRNA) molecules, can serve as a platform for building larger, multifunctional nanoparticles, says Guo, which can then be injected into the body to deliver therapeutics to targeted cells.
"RNA nanoparticles have applications in treating cancers and viral infections," he says, "but one of the problems in the field is that RNA nanoparticles are relatively unstable. Without covalent bonds or cross-linking to keep them together, the nanoparticles produced via self assembly can dissociate when injected into animal and human circulation systems, where they exist at very low concentrations."
In the work, Guo and researchers explored the unique structure of the DNA packaging motor of bacteriophage phi29, a virus that infects bacteria. The motor is geared by a ring of pRNA molecules containing interlocking loops and helical domains, which are joined together by a strong 3WJ motif.
"The pRNA is extraordinary strong," says Guo, "since it is a mechanical part that nature uses to gear a powerful motor. This strength makes it an ideal platform for constructing RNA nanoparticles. Furthermore, the core has unique and unusually stable features, such as resistance to strong denaturants like urea and the ability remains intact at ultra-low concentrations in the absence of magnesium."
Using three small fragments of RNA with high affinity for assembling into larger structures, researchers were able to recreate the 3WJ core outside the pRNA structure. In addition, each arm of the 3WJ core can be fused to siRNA molecules, receptor-binding ligands and RNA aptamers, molecular tools necessary for the nanoparticle to find a targeted cell inside the body and silence genes within it.
The resulting nanoparticle remained stable and functional in vitro and, when introduced in vivo, targeted tumors specifically without diffusing to other critical organs or normal tissues.
"Making fusion complexes of DNA or RNA is not hard," says Guo, "but ensuring the appropriate folding of individual modules within the complex to retain their function after fusion is a difficult task. The pRNA 3WJ core directs the folding of individual functional modules, and the stability of the 3WJ core ensures that each fusion module remain folded for proper function."
Earlier this year, Guo and his team overcame another obstacle to RNA nanotechnology, the risk posed by RNase, a common enzyme that quickly degrades RNA upon contact. By replacing a chemical group in RNA's ribose ring, Guo's team was able to make the RNA resistant to degradation, while retaining its ability to assemble into nanoparticles and form appropriate 3D structure and function.
Guo has pioneered RNA nanotechnology since 1998, when his lab discovered that RNA nanoparticles in the bacteriophage phi29 virus can be constructed by self-assembly using re-engineered fragments to gear a nanomotor to power DNA into the virus protein shell.
He serves as director of UC's National Institutes of Health (NIH) Nanomedicine Development Center, and director of the Cancer Nanotechnology Platform Partnership Program at UC, funded by the National Cancer Institute.
This research was supported by the National Institute of General Medical Sciences, National Institutes of Health.
Co-authors include Dan Shu, Yi Shu and Farzin Haque at UC and Sherine Abdelmawla at Kylin Therapeutics, Inc. Guo is a co-founder of Kylin Therapeutics, Inc.
Katy Cosse | EurekAlert!
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences