Laser activates gene therapy in rats' eyes

Health 21 November 2005

Laser light has been used to remotely control gene therapy in rats. This mechanism will help make gene therapy more effective by allowing the precise time and location at which new genes are activated to be controlled, meaning specific tissues can be targeted while healthy tissues are left alone.

Lasers have been used in the past to perforate cells for gene therapy in cultured cells. But the new research – activating marker genes in the eyes of rats – is more sophisticated and the first time lasers have been used for gene therapy in live animals.

Kazunori Kataoka, at the University of Tokyo, Japan, and colleagues developed a photosensitive molecular complex that could be activated in rats’ eyes by irradiating them with visible light from a low power laser.

The synthetic complex is designed to deliver foreign DNA by carrying it past the cell membrane – a process known as transfection. The complex consists of three components: a photosensitive anionic dendrimer, which provides the triggering mechanism, and a cationic peptide which drives the third component, its DNA payload, towards the nucleus of a cell after it has been released.


The complex enters the cell by a process known as endocytosis, where the cell’s plasma membrane envelops the complex at its surface and draws it into the cell. The membrane around the complex then detaches from the cell’s membrane to form a bubble containing the complex within the cell.

Applying the pulse of the laser light causes the dendrimer to break free from its bubble and simultaneously release the DNA-carrying peptide. By only causing damage to the plasma enveloping the complex the cell membrane is left intact, reducing cell death.

Light delivery

Jennifer West at Rice University in Houston, Texas, US, has used light to kill cancer cells by inducing localised heating in nanoparticles. She says that the scope of such “biophotonics” does not have to be limited to exposed areas such as the eye.

“Some wavelengths of light can penetrate very deeply,” she says. Near-infrared, for example, could potentially be used to treat many different tissue types and organs. And fibre optics can be run through needles, catheters and laparoscopes to deliver light of any wavelength to essentially anywhere in the body.

But there are good reasons for concentrating on ocular therapies, says Christopher Norbury at Pennsylvania State University, US. There is a lot of interest in using gene therapy to treat congenital blindness because gene therapy has a greater chance of success in the eye compared with other parts of the body.

There are two reasons why gene therapy often does not work, says Norbury. “Either because the cells are dividing so the gene isn’t passed on or because you get an immune response against the gene.” But in the eye, cells tend not to divide and immune responses are less severe.

Norbury also notes that previous methods of breaking into cells often kill a lot of them. But, according to the Japanese researchers, evaluations of the complex carried out on cultured cells showed that, not only did the areas targeted by laser light enhance gene expression 100-fold, but cell death in those areas was minimal.

Journal reference: Nature Materials (DOI: 10.1038/nmat1524)