Lentiviral vectors, two decades later

In the mid-1990s, several years after a variety of viral vectors started being used for gene transfer into cells, tissues, and in some cases humans, it became clear that there were considerable limitations ( 1 ). For applications requiring a stable genetic modification that could lead to sustained gene expression in cells and their progeny, a delivery vehicle was needed that could transduce foreign cargo into dividing and nondividing cells, without causing immuno- or genotoxicity. A decade earlier, human immunodeficiency virus (HIV) had been identified as the cause of AIDS, and rapid studies of its biology led to the idea that this genus of retrovirus—lentiviruses—could be optimized for gene therapy.