Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

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

Performance Drop in Solar Cells Prevented by Nanotechnology February 1st, 2015

Pinholes are Pitfalls for High Performance Solar Cells February 1st, 2015

New method allows for greater variation in band gap tunability: The method can change a material's electronic band gap by up to 200 percent January 31st, 2015

DNA nanoswitches reveal how life's molecules connect: An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs January 30th, 2015

Imaging

Park Systems Announces Innovations in Bio Cell Analysis with the Launch of Park NX-Bio, the only 3-in-1 Imaging Nanoscale Tool Available for Life Science Researchers January 29th, 2015

2015 Nanonics Image Contest January 29th, 2015

JPK opens new expanded offices in Berlin to meet the growing demand for products worldwide January 28th, 2015

Pittcon News: Renishaw adds to the comprehensive imaging options available with its inVia confocal Raman microscope January 27th, 2015

Govt.-Legislation/Regulation/Funding/Policy

Evidence mounts for quantum criticality theory: Findings bolster theory that quantum fluctuations drive strange electronic phenomena January 30th, 2015

Nanoscale Mirrored Cavities Amplify, Connect Quantum Memories: Advance could lead to quantum computing and the secure transfer of information over long-distance fiber optic networks January 28th, 2015

Detecting chemical weapons with a color-changing film January 28th, 2015

'Bulletproof' battery: Kevlar membrane for safer, thinner lithium rechargeables January 28th, 2015

Nanomedicine

DNA nanoswitches reveal how life's molecules connect: An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs January 30th, 2015

Made-in-Singapore rapid test kit detects dengue antibodies from saliva: IBN's MedTech innovation simplifies diagnosis of infectious diseases January 29th, 2015

Iranian Researchers Planning to Produce Edible Insulin January 28th, 2015

Nanoparticles that deliver oligonucleotide drugs into cells described in Nucleic Acid Therapeutics January 28th, 2015

Discoveries

Performance Drop in Solar Cells Prevented by Nanotechnology February 1st, 2015

Pinholes are Pitfalls for High Performance Solar Cells February 1st, 2015

New method allows for greater variation in band gap tunability: The method can change a material's electronic band gap by up to 200 percent January 31st, 2015

DNA nanoswitches reveal how life's molecules connect: An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs January 30th, 2015

Announcements

Performance Drop in Solar Cells Prevented by Nanotechnology February 1st, 2015

Pinholes are Pitfalls for High Performance Solar Cells February 1st, 2015

New method allows for greater variation in band gap tunability: The method can change a material's electronic band gap by up to 200 percent January 31st, 2015

DNA nanoswitches reveal how life's molecules connect: An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs January 30th, 2015

Nanobiotechnology

DNA nanoswitches reveal how life's molecules connect: An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs January 30th, 2015

Spider electro-combs its sticky nano-filaments January 28th, 2015

Nanoshuttle wear and tear: It's the mileage, not the age January 26th, 2015

Engineering self-assembling amyloid fibers January 26th, 2015

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







© Copyright 1999-2015 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE