Researchers have developed a general technique for specific gene targeting using a mobile bacterial intron that copies itself into genomic DNA (Science 289, 452–457, 2000). The group II intron from Lactococcus lactis is a catalytic RNA that splices itself out of an RNA transcript with the help of an intron-encoded protein (IEP). The excised intron—bound to the IEP—then inserts into the genome at a particular sequence and is reverse transcribed by the IEP into cDNA. To better understand the rules of target-site recognition, the researchers devised a genetic assay that could measure the contribution of individual nucleotides in the recipient DNA to intron mobility, and found they could redirect the intron by mutating a small region expected to base-pair with the target. They also selected introns capable of inserting at a desired destination from a combinatorial library of randomized sequences. The researchers have achieved integration into bacterial genomes and are now taking aim at eukaryotic chromosomes. “If the technique can be made to work for chromosomal insertion in human cells, then the full range of gene therapy applications would become possible,” says senior author Alan Lambowitz.