The inside out of lentivirus vectors

Lentivirus Lentiviruses owe their name (lenti means slow in latin) to the long period of time elapsing between the initial infection and the onset of the disease, that can protract over a period of months or even years. Viruses belonging to the Lentivirus genus are present in primates, ungulates (horse, cattle, sheep and goat) and felids (cat). Primates are the natural host for several lineages of closely related simian and human immunodeficiency viruses (SIV and HIV) that are the causative agents of acquired immunodeficiency syndrome (AIDS).

Lentivirus vectors bears an obvious advantage over other retrovirus vectors in that they offer the possibility to efficiently target non-dividing and differentiated cells, such as neurons. Paradoxically, the use of retrovirus vectors is hindered by the same process that makes them interesting for gene therapy, i.e., integration. This process is largely nonspecific and, as it has been shown in vivo, may either be of no consequence to the cell or lead to serious drawbacks. Although this problem may in theory be minimized in gene therapy applications targeting terminally differentiated cells, the problem of integration is serious. To this end, a number of alternative strategies have been developed, ranging from the redirection of retrovirus integration to particular chromosomal locations, to the ablation of the integration process altogether. Although in its infancy, the efforts to redirect retrovirus integration must be pursued and researchers may possibly transpose to lentiviruses a mechanism of specific integration used by other viruses.

The Inside Out of Lentiviral Vectors. (2011) Viruses 3(2): 132-159; doi:10.3390/v3020132
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them.


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