Carbon nanotubes offer a new approach to gene therapy

Many genes that are related to particular diseases have now been identified. Scientists are trying to use this knowledge to treat diseases.

It is thought that defective or missing genes could be replaced by introducing the relevant gene into cells from the outside. This is not so simple, because DNA cannot easily pass through cell membranes; it needs a transporter, such as a virus, liposome, or special peptide. A European team of researchers has now developed a new approach: they have succeeded in slipping DNA into mammalian cells by using modified carbon nanotubes.

Carbon nanotubes are tiny needle-shaped structures made exclusively of carbon atoms. They can be pictured as one or more layers of a rolled up sheet of graphite. They have become the focus of much interest as materials for biomedicine as well as other technical applications.

In order to work as gene transporters, however, the tiny "needles" first need to be slightly modified. The Italian, French, and British team led by Alberto Bianco (Strasbourg), Kostas Kostarelos (London), and Maurizio Prato (Trieste) attached several chains made of carbon and oxygen atoms to the outside of carbon nanotubes. The end of each chain consists of a positively charged amino group (– NH3+). This alteration makes the tiny needles water-soluble. More importantly, the charged groups are very attractive to the negatively charged phosphate groups in the DNA backbone. By using these electrostatic attractive forces, the researchers were able to solidly anchor plasmides, small, ring-shaped DNA fragments from bacteria, to the outsides of the nanotubes. They then brought their DNA – nanotube hybrids into contact with a cell culture of mammalian cells. The result: the carbon nanotubes, together with their DNA cargo, entered into the cells. Electron microscope images of thin sections of the cells even showed how the thin needles make their way through the cell membrane. They are not harmful to the cells because, unlike several previous gene-transport systems, they do not destabilize the membrane when passing through it. Once inside the cell, the genes proved to be functional.

Carbon nanotubes are not limited to the transfer of genes; other modifications should also allow for the attachment of other pharmaceuticals, allowing them to enter cells as well.

http://www.wiley.com, http://www.angewandte.org