Nanodisk gene therapy

January 13, 2011

A team of scientists at the Universitat Autonoma de Barcelona (UAB) has demonstrated that the peptide R9, formed by a specific type of amino acid (arginine), can encapsulate genetic material, assemble itself with other identical molecules to form nanoparticles, and enter directly into the cell nucleus to release the material it contains. The nanoparticles have the shape of a disk, with a diameter of 20 nm. and a height of 3 nm.

One of the challenges of gene therapy — a set of methodologies aimed at treating several nucleic acid diseases (DNA or RNA) — is to assure that this material arrives directly to the nucleus of the cell without losing a substantial amount along the way and without producing any undesired side effects. With this aim, scientists experiment with the use of different types of vectors, molecules capable of transporting genetic material to the correct place. Presently, natural “deactivated” viruses are the most commonly used vectors in clinical trials, their side effects however often limit therapeutic application.

One of the most promising alternatives in this field is the use of artificial viruses. These viruses can be constructed through genetic engineering by assembling minute protein structures made up of peptides, the building blocks of proteins.

The study was published recently in the journals Biomaterials and Nanomedicine and describes how scientists studied the performance of R9 nanodisks in the interior of the cells using confocal microscopy techniques provided by the UAB. The images show that once the cell membrane is passed, particles travel directly to the nucleus at a rate of 0.0044 micrometers per second, ten times faster than if they dispersed passively in the interior. Nanoparticles accumulate in the interior of the nucleus and not in the cytoplasm and therefore increase their level of effectiveness.

The discovery represents a new category of nanoparticles offering therapeutic benefits. According to Dr Esther Vázquez, director of the project, “nanodisks assemble automatically, move rapidly, remain stable and travel to the interior of the nucleus. This makes them a promising tool as a prototype for the safe administration of nucleic acids and functional proteins.”

Adapted from materials provided by the Universitat Autonoma de Barcelona