Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Using Nanoparticles, In Vivo Gene Therapy Activates Brain Stem Cells

26.07.2005


Technique may allow scientists to repair brain cells damaged by disease, trauma or stroke



Using customized nanoparticles that they developed, University at Buffalo scientists have for the first time delivered genes into the brains of living mice with an efficiency that is similar to, or better than, viral vectors and with no observable toxic effect, according to a paper published this week in Proceedings of the National Academy of Sciences.

The paper describes how the UB scientists used gene-nanoparticle complexes to activate adult brain stem/progenitor cells in vivo, demonstrating that it may be possible to "turn on" these otherwise idle cells as effective replacements for those destroyed by neurodegenerative diseases, such as Parkinson’s.


In addition to delivering therapeutic genes to repair malfunctioning brain cells, the nanoparticles also provide promising models for studying the genetic mechanisms of brain disease.

"Until now, no non-viral technique has proven to be as effective as the viral vectors in vivo," said co-author Paras N. Prasad, Ph.D., executive director of the UB Institute for Lasers, Photonics and Biophotonics, SUNY Distinguished Professor in UB’s Department of Chemistry and principal investigator of the institute’s nanomedicine program. "This transition, from in vitro to in vivo, represents a dramatic leap forward in developing experimental, non-viral techniques to study brain biology and new therapies to address some of the most debilitating human diseases."

Viral vectors for gene therapy always carry with them the potential to revert back to wild-type, and some human trials have even resulted in fatalities.

As a result, new research focuses increasingly on non-viral vectors, which don’t carry this risk.

Viral vectors can be produced only by specialists under rigidly controlled laboratory conditions. By contrast, the nanoparticles developed by the UB team can be synthesized easily in a matter of days by an experienced chemist.

The UB researchers make their nanoparticles from hybrid, organically modified silica (ORMOSIL), the structure and composition of which allow for the development of an extensive library of tailored nanoparticles to target gene therapies for different tissues and cell types.

A key advantage of the UB team’s nanoparticle is its surface functionality, which allows it to be targeted to specific cells, explained Dhruba J. Bharali, Ph.D., a co-author on the paper and post-doctoral associate in the UB Department of Chemistry and UB’s Institute for Lasers, Photonics and Biophotonics.

While they are easier and faster to produce, non-viral vectors typically suffer from very low expression and efficacy rates, especially in vivo.

"This is the first time that a non-viral vector has demonstrated efficacy in vivo at levels comparable to a viral vector," Bharali said.

In the UB experiments, targeted dopamine neurons -- which degenerate in Parkinson’s disease, for example -- took up and expressed a fluorescent marker gene, demonstrating the ability of nanoparticle technology to deliver effectively genes to specific types of cells in the brain.

Using a new optical fiber in vivo imaging technique (CellviZio developed by Mauna Kea Technologies of Paris), the UB researchers were able to observe the brain cells expressing genes without having to sacrifice the animal.

Then the UB researchers decided to go one step further, to see if they could not only observe, but also manipulate the behavior of brain cells.

Their finding that the nanoparticles successfully altered the development path of neural stem cells is especially intriguing because of scientific concerns that embryonic stem cells may not be able to function correctly since they have bypassed some of the developmental stages cells normally go through.

"What we did here instead was to reactivate adult stem cells located on the floor of brain ventricles, germinal cells that normally produce progeny that then die if they are not used," said Michal K. Stachowiak, Ph.D., co-author on the paper and associate professor of pathology and anatomical sciences in the UB School of Medicine and Biomedical Sciences. Stachowiak is in charge of in vivo studies at the UB Institute for Lasers, Photonics and Biophotonics.

"It’s likely that these stem/progenitor cells will grow into healthy neurons," he said.

"In the future, this technology may make it possible to repair neurological damage caused by disease, trauma or stroke," said Earl J. Bergey, Ph.D., co-author and deputy director of biophotonics at the institute.

The group’s next step is to conduct similar studies in larger animals.

The UB research was supported by the John R. Oishei Foundation, the National Science Foundation, the American Parkinson Disease Association and UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.

Research at UB’s Institute for Lasers, Photonics and Biophotonics has been supported by special New York State funding sponsored by State Sen. Mary Lou Rath.

Ellen Goldbaum | EurekAlert!
Further information:
http://www.buffalo.edu

More articles from Life Sciences:

nachricht Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>