Scientists have literally thrown light on the problem of gene targeting. Using a two-photon scanning laser microscope, scientists at the University of California Irvine and the University of California San Diego have performed targeted gene inactivation in cultured cells (PNAS 97, 9504–9507, 2000). Using a conveniently flat line of cultured PTK2 cells, the researchers were able to visualize the chromosomal loci containing the ribosomal DNA. A DNA-associating dye was added to the cells to make the chromosomes photosensitive, and the ribosomal DNA locus was inactivated by precisely aiming the focal point of the two-photon microscope. All of the cells survived the treatment, which reliably knocked out the targeted locus. The authors argue that existing techniques, such as fluorescence in situ hybridization, should allow the same technique to be used on virtually any gene for which specific probes are available. Michael Berns, first author on the paper, says that the multiphoton-targeted gene inactivation approach “could be used on most standard two-photon microscopes,” allowing researchers to apply it almost immediately.