Lentivirus: A Vector for Nervous System Applications
Vectors based on lentiviruses are opening up new approaches for the treatment of neurological disease and damage. They efficiently deliver genes into many different types of primary neurons from a broad range of species including human, and the resulting gene expression is longterm and non-toxic. Numerous animal studies have now been undertaken with these vectors, and correction of disease models has been obtained. These vectors have been refined to a very high level, and they are now ready for clinical evaluation (reviewed in Martin-Rendon et al. 2001; Deglon and Aebischer 2002). This review will describe the general features of lentiviral vectors with particular emphasis on vectors derived from the non-primate lentivirus, equine infectious anaemia virus (EIAV), then give some key examples of gene transfer and genetic correction in animal models of neurological diseases. The prospects for the clinical evaluation of lentiviral vectors for the treatment of human neurological disease will be outlined.
KeywordsHuman Immunodeficiency Virus Motor Neuron Dorsal Root Ganglion Long Terminal Repeat Motor Neuron Disease
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- Azzouz M, Martin-Rendon E, Barber RD et al (2002) Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson’s disease. J Neuro 22: 10302–10312Google Scholar
- Kim VN, Mitrophanous K, Kingsman SM et al (1998) Minimal requirement for a lentivirus vector based on human immunodeficiency virus type J Virol 72: 811–816Google Scholar
- Lo Bianco C, Ridet JL, Schneider BL et al (2002) a-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson’s disease. Proc Natl Acad Sci USA 99: 10813–10818Google Scholar
- Miller AD (1997) Development and applications of retroviral vectors. In Coffin JM, Hughes SH, Varmus HE (eds) Retroviruses. Cold Spring Harbor Press, New York, pp 437–473Google Scholar
- Otto E, Jones-Trower A, Vanin EF et al (1994) Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis. J Virol 68: 4241–4250Google Scholar
- Powell JS et al (2001) Phase I trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous injection. Thromb Haemost 86:0C2489Google Scholar
- Watson DJ, Kobinger GP, Passini MA et al (2002) Targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins. Mol Ther 5: 528–537Google Scholar
- Weber E, Anderson WF, Kasahara N et al (2001) Recent advances in retrovirus vector-mediated gene therapy: teaching an old vector new tricks. Curr Opin Mol Ther 5: 439–453Google Scholar