Development of Foamy Virus Vectors

Retroviral vectors developed from the murine leukemia virus (MLV) were the first and most widely used vectors for gene transfer experiments (1 ). Delineation of their replication strategy allowed extensive manipulation of their genome and the development of vector packaging cell lines; the latter provide a reliable tool for the production of high titer vector stocks and have been key to the popularity of MLV-type vectors (2 ). Because integration into the host cell genome is a sine qua non of the retroviral life cycle, MLV-type vectors were extensively used to transduce hematopoietic stem cells (HSCs) where stable genomic integration allows transmission of a gene to the differentiated progeny cells (3 –5 ). However, a number of problems with these vectors have limited their use in the clinical setting; low transduction rates on primate and human HSCs, complete dependence on cell division for integration and silencing of the transferred gene are the major problems with the MLV-type vectors (6 –8 ). In an effort to address these issues, two other retro viruses have been explored for their gene transfer potential; lentiviruses, like the human immunodeficiency virus (HIV) and, to a lesser extent, foamy (or spuma) viruses (9 ,10 ). Although many details of HIV biology have been unveiled owing to the extensive research on the HIV-related human diseases, relatively little is known about the foamy viruses. As a result, foamy vectors have not yet been as extensively developed as HIV and MLV-type vectors.