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!
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy