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Gene therapy lentiviruses

To circumvent this problem, vectors that are based on lentiviruses have been developed. In contrast to prototypic retroviruses, lentiviruses do not require cell division for integration. Gene-therapy vectors have been developed from a broad spectrum of lentiviruses including human immunodeficiency vims (HIV), simian and feline immunodeficiency vims as well as visna/maedi vims. The most widely used lentiviral vector system is based on HIV-1. These vectors can efficiently transduce a broad spectrum of dividing and nondividing cells including neurons, hepatocytes, muscle cells, and hematopoietic stem cells [1,2]. [Pg.532]

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. [Pg.334]

Lentiviruses can be very effective vectors for gene therapy since they can change the expression of genes in target cells for up to 6 months. They are useful for nondividing and terminally differentiated cells including muscle cells, hepato-cytes, neurons, macrophages, retinal photoreceptors and hematopoietic stem cells. However, lentiviruses cannot enter quiescent cells in which reverse transcription is blocked. [Pg.233]

Bjorklund, A. et al. (2000). Towards a neuroprotective gene therapy for Parkinson s disease Use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res. 886(1-2), 82-98. [Pg.214]

Among the viruses widely used for gene therapy are those used to obtain heterologous proteins from animal cells, particularly RNA viruses (retrovirus and lentivirus) and DNA viruses (adenovirus, adeno-associated viruses, and herpesvirus). Table 21.1 summarizes the advantages and disadvantages of each virus as a carrier in gene therapy. [Pg.492]

The lentiviral vectors have safety concerns similar to the retroviral vector-based gene therapy products (1) the production of a replication competent lentivirus (RCL) during manufacturing and (2) the potential for insertional mutagenesis, resulting in oncogene activation. One concern unique to the lentiviral vectors is the possibility that the vector can be mobilized in vivo,... [Pg.725]

The first viral vector systems were developed more than 25 years ago [9], and since then viral gene therapy strategies has been progressively developed [10]. A variety of virus vectors has been employed and modified to deliver genes to cells to provide either transient, such as adenovirus [11-13], poxviruses (vaccinia) [14], or herpes virus [15], or permanent, such as retroviruses (lentivirus) [16-18] and adeno-associated virus [19], transgene expression each approach has its characteristic advantages and disadvantages. [Pg.1152]


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