The piggyBac transposon holds promise for human gene therapy.

Abstract

Ever since their molecular isolation in eukaryotic organisms, transposons have been precious implements of the geneticist's toolkit. The properties that make transposons so useful are their ability to move from one chromosomal position to another and the relatively minimal requirements for transposition to occur in the test tube and in living cells (1). In particular, transposons can be harnessed to stably integrate sizeable pieces of DNA into a host's chromosome (2, 3). This quality provides a tremendous potential for transgenesis and large-scale insertional mutagenesis. Transposon-mediated DNA delivery, although first limited to a small number of invertebrate species, has become progressively more applicable to vertebrates, including mammalian cells (3–5). This progress has opened the door to the development of a new generation of vectors for human gene therapy and mammalian forward genetics that are potentially more easily controlled, more versatile, and safer than viral vectors (5). However, applications of transposon vectors for clinical trials in gene therapy, and the predictable manipulation of mammalian genomes, have been hindered by their low integration efficiency relative to viral vectors. In this issue of PNAS, Wu et al. (6) move one step further in the quest for a superior gene delivery tool in mammals. They identified piggyBac (PB) as the most active and flexible transposon system yet tested for transformation of mammalian cells.