Human Immunodeficiency Virus Type 1-Based Vectors for Gene Delivery to Human Hematopoietic Stem Cells

A number of inherited and acquired disorders can potentially be treated by gene-based therapies. To be successful, gene therapy requires efficient delivery and continued expression of the therapeutic gene in the target cell. Toward this goal, a variety of methods have been developed for delivering genes into various cell types and tissues (for reviews, see refs. 1 and 2 ). Common viralbased methods utilize vectors derived from oncoretroviruses, adenovirus type 5, adenoassociated virus type 2, herpes simplex virus type 1 (HSV-1), and, most recently, lentiviruses. Among these, oncoretroviral vectors (primarily those based on Moloney murine leukemia virus) have been the most widely used to date in gene therapy applications, mainly because of their capacity to stably integrate into cellular DNA in the absence of wild-type virus (3 –5 ). However, a major limitation of oncoretroviral vectors is their inability to transduce nondividing cells (6 –9 ).