Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team finds stable RNA nano-scaffold within virus core

13.09.2011
With the discovery of a RNA nano-scaffold that remains unusually stable in the body, researchers at the University of Cincinnati (UC) have overcome another barrier to the development of therapeutic RNA nanotechnology.

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!
Further information:
http://www.uc.edu

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>