Lentiviral vector

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]. 

To address biosafety concerns, self-inactivating lentiviral vectors and stable packaging cell lines have been developed. 

Finally, lentiviral vectors have been shown to transduce human embryonic stem cells. Therefore, this type of gene-therapy vector might also be used in stem cell-based therapies. 

Levine BL, Humeau LM, Boyer J et al (2006) Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci USA 103(46) 17372-17377... 

Li MJ, Kim J, Li S, Zaia J, Yee JK, Anderson J, Akkina R, Rossi JJ (2005b) Long-term inhibition of HlV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 12 900-909... 

For intracellular immunization strategies of hepatitis B and C, lentiviral vectors have been tested (Matskevich et al. 2003 Parouchev et al. 2006). However, as the turnover of hepatocytes is thought to be much slower than that of HPC or T cells, nonintegrating vectors that carry a reduced risk of insertional mutagenesis are favored (Nowak et al. 1996). 

Mautino MR, Morgan RA (2000) Potent inhibition of human immunodeficiency virus type 1 reph-cation by conditionally replicating human immunodeficiency virus-based lentiviral vectors expressing envelope antisense mRNA, Hum Gene Ther 11 2025-2037... 

Nash KL, Alexander GJ, Lever AM (2005) Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and hammerhead libozymes. J Viral Hepat 12 346-356... 

Guenechea G, Gan Of, Inamitsu T, et al. Transduction of human CD34+ GD38 bone marrow and cord blood derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther. 2000 1 566 573. 

Vigna, E., Naldini, L. (2000). Lentiviral vectors excellent tools for experimental gene transfer and promising candidates for gene therapy. J. Gene Med., 2, 308-316. 

Kafri, T., Blomer, U., Peterson, D.A., Gage, F.H., Verma, I.M. (1997). Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat. Genet., 17, 314-317. 

Follenzi, A. (2002). Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum. Gene Then, 13, 243-260. 

Logan, A.C., Lutzko, C., Kohn, D.B. (2002). Advances in lentiviral vector design for gene-modification of hematopoietic stem cells. Cunn. Opin. Biotechnol., 13(5), 429 136. 

Tonini, T., Claudio, P.P., Giordano, A., Romano, G. (2004). Retroviral and lentiviral vector titration by the analysis of the activity of viral reverse transcriptase. Methods Mol. Biol., 285, 155-158. 

Philpott NJ, Thrasher AJ. 2007. Use of nonintegrating lentiviral vectors for gene therapy. Hum Gene Ther. 18 483-489. 

Woods NB, Ooka A, Karlsson S. 2002. Development of gene therapy for hematopoietic stem cells using lentiviral vectors. Leukemia. 16 563-569. 

Mautino, M.R., Reiser, N. and Morgan, R.A. (2000) Improved titers of HIV-based lentiviral vectors using the SRV-1 constitutive transport element. Gene Ther., 7,1421-1424. 

Ramezani, A., Hawley, T.S. and Hawley, R.G. (2000) Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol. Ther., 2,458 169. 

Salmon, P., Kindler, V., Ducrey, O., Chapuis, B., Zubler, R.H. and Trono, D. (2000) High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood, 96, 3392-3398. 

The preferred method for delivery of lentiviral vectors is microinjection into the perivitelline space of single cell or cleavage-stage embryos, which is a far less invasive procedure... 

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