The Hackett Lab has focused on engineering of genomes since its inception in 1980. Early projects involved re-engineering genomes of Rous sarcoma virus to elucidate the roles of viral RNA in the virus life cycle. This engineering expertise led in the mid 1980s to engineering genomes of fish - first zebrafish as a model system and subsequently larger game fish including northern pike, walleye and salmonids. This work inspired two lab members, Drs. Zsuzanna Izsvak and Zoltan Ivics to resurrect the Sleeping Beauty (SB) transposon system from salmonid genomes as a method for efficiently introducing genetically engineered expression cassettes into vertebrate genomes. The first SB transposes and transposons were based on extinct Tc1/Mariner transposons found in modern fish. Developed in 1997, Sleeping Beauty is the most widely used transposon for mammalian applications. The Hackett Lab has shown that the Sleeping Beauty transposon system can treat mucopolysaccharidosis (MPS) diseases in mouse models, including alpha-1-iduronidase deficiency (MPS I) and beta-glucuronidase deficiency (MPS VII). Current projects focus on scaling up delivery to dogs as a pre-clinical model for humans and methods for directing SB transposons to specific chromosomal locations. In collaboration with others, Sleeping Beauty is being used as a vector to treat other human deseases, including hemophilia and B-cell lymphoma.