Nanotech News

August 8, 2005

Delivering and Expressing Genes in the Brain

Using customized silica nanoparticles, investigators from the University at Buffalo 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 effects. This work was led by Paras Prasad, Ph.D.

Nanoparticles allow cells on the floor of a mouse brain ventricle to express the gene for green fluorescent protein. Courtesy of Paras N. Prasad, Ph.D. University of Buffalo

Writing in the Proceedings of the National Academy of Science USA, the University of Buffalo team described how they modified silica nanoparticles that they had created previously so that the particles would tightly bind DNA molecules. The researchers then injected the particles into specific locations within the brains of laboratory mice and observed that the DNA carried by the nanoparticles was able to activate adult brain stem/progenitor cells in the living animals.

In addition to delivering therapeutic genes to treat brain cancers and 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 Dr. Prasad. "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."

The 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 this particular type of nanoparticle is its surface functionality, which allows it to be targeted to specific cells.

In their experiments, the investigators created nanoparticles targeted to dopamine neurons - which degenerate in Parkinson's disease, for example. The dopamine neurons 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 investigators were able to observe the brain cells expressing genes without having to sacrifice the animal.

This work is detailed in a paper titled, "Organically modified silica nanoparticles: A nonviral vector for in vivo gene delivery and expression in the brain." An investigator from the Medical University of Gdansk, Poland, also contributed to this study. The full-text paper is available at the journal's website.
View abstract.