Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Building From the Ground Up, Researchers Construct RNA Nanoparticles to Safely Deliver Long-Lasting Therapy to Cells

Peixuan Guo, PhD, Dane and Mary Louise Miller Endowed Chair in biomedical engineering with students in his lab at the Vontz Center for Molecular Studies.

Credit: University of Cincinnati
Peixuan Guo, PhD, Dane and Mary Louise Miller Endowed Chair in biomedical engineering with students in his lab at the Vontz Center for Molecular Studies.

Credit: University of Cincinnati

Abstract:
Nanotechnology researchers have known for years that RNA, the cousin of DNA, is a promising tool for nanotherapy, in which therapeutic agents can be delivered inside the body via nanoparticles. But the difficulties of producing long-lasting, therapeutic RNA that remains stable and non-toxic while entering targeted cells have posed challenges for their progress.

Building From the Ground Up, Researchers Construct RNA Nanoparticles to Safely Deliver Long-Lasting Therapy to Cells

Cincinnati, OH | Posted on April 22nd, 2011

In two new publications in the journal Molecular Therapy, University of Cincinnati (UC) biomedical engineering professor Peixuan Guo, PhD, details successful methods of producing large RNA nanoparticles and testing their safety in the delivery of therapeutics to targeted cells.

The articles, in advance online publication, represent "two very important milestones in RNA nanotherapy," says Guo.

"One problem in RNA therapy is the requirement for the generation of relatively large quantities of RNA," he says. "In this research, we focused on solving the most challenging problem of industry-scale production of large RNA molecules by a bipartite approach, finding that pRNA can be assembled from two pieces of smaller RNA modules."

Guo, Dane and Mary Louise Miller Endowed Chair of biomedical engineering, serves as director of the National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Program at UC. He has focused his research on RNA for decades, pioneering its use as a versatile building block for nanotechnology, or for the engineering of functional systems at the molecular scale. In 1987, he discovered a packaging RNA (pRNA) in the bacteriophage phi29 virus which can gear a motor to package DNA into the viral protein shell. In 1998, his lab discovered that pRNA can self-assemble or be engineered into nanoparticles to gear the motor.

In his most recent research, Guo and colleagues detail multiple approaches for the construction of a functional 117-base pRNA molecule containing small interfering RNA (siRNA). siRNA has already been shown to be an efficient tool for silencing genes in cells, but previous attempts have produced chemically modified siRNA lasting only 15-45 minutes in the body and often inducing undesired immune responses.

"The pRNA particles we constructed to harbor siRNA have a half life of between five and 10 hours in animal models, are non-toxic and produce no immune response," says Guo. "The tenfold increase of circulation time in the body is important in drug development and paves the way towards clinical trials of RNA nanoparticles as therapeutic drugs."

Guo says the size of the constructed pRNA molecule is crucial for the effective delivery of therapeutics to diseased tissues.

"RNA nanoparticles must be within the range of 15 to 50 nanometers," he says, "large enough to be retained by the body and not enter cells randomly, causing toxicity, but small enough to enter the targeted cells with the aid of cell surface receptions.

In the paper, "Assembly of Therapeutic pRNA-siRNA Nanoparticles Using Bipartite Approach," Guo and his colleagues used two synthetic RNA fragments to create the 117-base pRNA, which was able to further assemble with other pRNA molecules and function in the bacteriophage phi29 viral motor to package DNA.

"The two-piece approach in pRNA synthesis overcame challenges of size limitations in chemical synthesis of RNA nanoparticles," Guo wrote. "The resulting nanoparticles were competent in delivering and releasing therapeutics to cells and silencing the genes within them. The ability to chemically synthesize these nanoparticles allows for further chemical modification of RNA for stability and specific targeting."

The second publication, "Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery," builds on that research, demonstrating that modified three-dimensional pRNA nanoparticles were readily manufactured through the two-piece approach. The modified nanoparticles were resistant to common enzymes that can attack and degrade RNA and remained chemically and metabolically stable.

Furthermore, when delivered to target cells in an animal model, the nanoparticles were non-toxic and did not induce an immune response, enabling the nanoparticles to bind to cancer cells in vivo.

Previous studies have encased therapeutic siRNA in a polymer coating or liposome for delivery to cells.

"To our knowledge, this is the first naked RNA nanoparticles to have been comprehensively examined pharmacologically in vivo and demonstrated to be safe, as well as deliver itself to tumor tissues by a specific targeting mechanism," he says. "It suggests that the pRNA nanoparticles without coating have all the preferred pharmacological features to serve as an efficient nanodelivery platform for broad medical applications."

Co-authors of "Assembly of Therapeutic pRNA-siRNA Nanoparticles Using Bipartite Approach" include Yi Shu, Mathieu Cinier, Sejal Fox and Nira Ben-Johnathan of the University of Cincinnati.

Co-authors of "Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery" include Sherine Abdelmawla and Songchuan Guo of Kylin Therapeutics and Purdue University, Limin Zhang, Sai M Pulukuri, Prithviraj Patankar, Patrick Conley, Joseph Trebley and Qi-Xiang Li of Kylin Therapeutics.

This study was funded by National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Institute of General Medical Sciences and Kylin Therapeutics Inc. Guo is co-founder of Kylin Therapuetics.

####

For more information, please click here

Contacts:
Katy Cosse
(513) 558-0207

Copyright © University of Cincinnati

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

Fewer defects from a 2-D approach August 15th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

Imaging

Industry’s First Dedicated Cryo-DualBeam System Automates Preparation of Frozen, Biological Samples: New Thermo Scientific Aquilos FIB/SEM protects sample integrity and enhances productivity for cryo-electron tomography workflow August 8th, 2017

Thermo Fisher Scientific Advances Cryo-EM Leadership to Drive Structural Biology Discoveries: New Thermo Scientific Krios G3i raises bar for performance, automation and time-to-results Breakthrough Thermo Scientific Glacios provides a cryo-EM entry path for a broader range of res August 8th, 2017

New Quattro Field Emission ESEM Emphasizes Versatility and Ease of Use: Thermo Scientific Quattro ESEM allows materials science researchers to study nanoscale structure in almost any material under a range of environmental conditions August 8th, 2017

Thermo Fisher Scientific’s New Talos F200i S/TEM Delivers Flexible, High-Performance Imaging: New compact S/TEM can be configured to meet specific imaging and analytical requirements for materials characterization in research laboratories August 8th, 2017

Govt.-Legislation/Regulation/Funding/Policy

2-faced 2-D material is a first at Rice: Rice University materials scientists create flat sandwich of sulfur, molybdenum and selenium August 14th, 2017

Engineers pioneer platinum shell formation process – and achieve first-ever observation August 11th, 2017

Moving at the Speed of Light: University of Arizona selected for high-impact, industrial demonstration of new integrated photonic cryogenic datalink for focal plane arrays: Program is major milestone for AIM Photonics August 10th, 2017

Sensing technology takes a quantum leap with RIT photonics research: Office of Naval Research funds levitated optomechanics project August 10th, 2017

Nanomedicine

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

JPK reports on how the University of Glasgow is using their NanoWizard® AFM and CellHesion module to study how cells interact with their surroundings August 2nd, 2017

Research team bends individual tetrapod nanostructures August 2nd, 2017

Discoveries

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Fewer defects from a 2-D approach August 15th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

2-faced 2-D material is a first at Rice: Rice University materials scientists create flat sandwich of sulfur, molybdenum and selenium August 14th, 2017

Announcements

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

Fewer defects from a 2-D approach August 15th, 2017

Scientists from the University of Manchester and Diamond Light Source work with Deben to develop and test a new compression stage to study irradiated graphite at elevated temperatures August 15th, 2017

Nanobiotechnology

Gold shines through properties of nano biosensors: Researchers discover that fluorescence in ligand-protected gold nanoclusters is an intrinsic property of the gold particles themselves August 16th, 2017

Two Scientists Receive Grants to Develop New Materials: Chad Mirkin and Monica Olvera de la Cruz recognized by Sherman Fairchild Foundation August 16th, 2017

JPK reports on how the University of Glasgow is using their NanoWizard® AFM and CellHesion module to study how cells interact with their surroundings August 2nd, 2017

Research team bends individual tetrapod nanostructures August 2nd, 2017

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project