HIV-1-Derived Lentiviral Vectors
2002; Springer Science+Business Media; Linguagem: Inglês
10.1007/978-3-642-56114-6_2
ISSN2196-9965
Autores Tópico(s)CRISPR and Genetic Engineering
ResumoThe primary vectors of choice for gene therapy applications have been oncoretroviruses due to their simple genetic organization and their ability to integrate into the host cell genome without incurring cellular toxicity (ANDERSON 1998). However, these vectors require cell division for integration to occur (MILLER et al. 1990) due to a requirement for nuclear envelope breakdown to allow entry of the viral integration complex into the nucleus (ROE et al. 1993). This presents a major obstacle for in vivo or ex vivo transduction of non-dividing cells such as neurons, hepatocytes, muscle fibres, quiescent lymphocytes, and haematopoietic stem cells, as these cells are either inaccessible by such vectors, or must be manipulated in potentially detrimental ways to facilitate cell division and vector integration. For this reason, interest in recent years has turned to lentiviruses, due to their ability to infect and integrate in certain types of non-dividing cells (WEINBERG et al. 1991; BUKRINSKY et al. 1993; LEWIS and EMERMAN 1994). One lentivirus on which much work has been focused to derive vectors for gene therapy has been HIV-1, as it is the best characterized of the lentiviruses. The remainder of this review will focus on the properties of HIV-1 that allow it to efficiently infect non-dividing cells, and on the development of progressively safer and more efficient HIV-1-derived vectors over the past few years.
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