Abstract
The human immunodeficiency virus (HIV) is classified as a retrovirus because of its RNA genome and the fact that it requires reverse transcriptase to convert it into DNA. This virus belongs to the lentivirinae subfamily and is able to infect quiescent cells but is better known for its association with acquired immunodeficiency syndrome (AIDS) and can be described as one of the most effective vectors for gene transfer. Biosafety concerns are present whenever viral vectors are employed but are particularly pertinent to the development of HIV-based vectors. Insertional mutagenesis and the production of new replication-competent viruses (RCV) have been pointed to as major problems, but experimental data have shown that safe protocols can be developed for their production and application. Virological, evolutionary, immunological and cell biology studies must be conducted jointly to allow the clinical use of HIV vectors. This review will focus on the general properties, production and applications of retrovectors in gene therapy, with particular emphasis on those based on HIV systems.
Highlights
The basic principle of gene therapy is the introduction of exogenous genetic material to correct or modify the cell functions
The identification of the appropriate therapeutic gene as well as the target cell are essential for successful gene therapy, identifying the most suitable gene transfer method for a determined group of target cells is of fundamental importance
The active transport of lentivirus provirus is in part mediated by nuclear localization sequences (NLS) and the formation of proteic transportation complexes dependent on accessory genes such as human immunodeficiency virus (HIV) vpr (Naldini et al, 1996a and b; Vodicka et al, 1998) or on mechanisms regulating retrotranscription, such as strand displacement present in the pre-integration complex (PIC) (Klarmann et al, 2003) (Figure 2)
Summary
The basic principle of gene therapy is the introduction of exogenous genetic material to correct or modify the cell functions. The development of methods for the delivery of therapeutic genes to specific target cells has been under intense investigation for the last decade (reviewed in Romano et al, 2000; Amalfitano and Parks, 2002). The identification of the appropriate therapeutic gene as well as the target cell are essential for successful gene therapy, identifying the most suitable gene transfer method for a determined group of target cells is of fundamental importance. The vectors used to transfer genes are basically classified as viral or non-viral, each presenting its own benefits and drawbacks. This review will focus on the general properties, production and applications of retrovectors, with emphasis on HIVbased vectors
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