Light switch

From Boston, at a meeting of the American Chemical Society

Switching off a gene is now as simple as flicking on a light.

Working with zebrafish, a favorite model organism for biologists, Ilya A. Shestopalov and his colleagues at Stanford University showed that, once activated by ultraviolet light, a molecule called a photocaged morpholino can dampen a specific gene.

The molecule is made up of two parallel strips. One strip is an antisense molecule, which binds tightly to protein-coding RNA to shut down protein production. The other strip is an inhibitor that prevents the antisense molecule from doing so.

A light-sensitive bond connects the two strips. A 10-second pulse of ultraviolet light breaks the bond, liberating the antisense strip and allowing it to clamp down on the target gene product.

The Stanford team made a photocage to inhibit the gene ntl, known colloquially as “no tail” for the effect when the gene malfunctions. The researchers injected the molecule into zebrafish embryos, which are transparent, and then zapped the developing fish with ultraviolet light. Sure enough, the fish developed without tails.

In further experiments, the team used a tiny, focused beam to dampen the gene in only a small section of the developing zebrafish. Tissue in that section grew into odd shapes.

The team is now developing photocage gene silencers activated by infrared light, which penetrates deeper into tissue, for use in organisms that aren’t transparent.