Retroviral vectors

Gene therapy uses cloned DNA in adeno or retroviral vectors to transduce host cells for longterm therapy of certain genetic disorders with defined... 

ModUch U, Bohne J, Schmidt M, von Kalle C, Knoss S, Schambach A, Baum C (2006) Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity. Blood 108 2545-2553... 

To, R. Y., and Neiman, RE., The potential for effective antisense inhibition of retroviral replication mediated by retroviral vectors. In Erickson R.P., Izant J.G., eds., Gene Regulation Biology of Antisense RNA and DNA. Raven Press, New York, 1992, pp. 261-271. 

A number of alternative approaches are being developed that may overcome some of these issues. Replication-defective retroviral vectors are available that will more consistently (a) deliver a chosen gene into cells and (b) ensure chromosomal integration of the gene. A second innovation is the application of nuclear transfer technology. 

Once assimilated by the cell, the exogenous nucleic acid must now travel/be delivered to the nucleus. In some cases, the mechanism by which this transfer occurs is understood, at least in part (e.g. in the case of retroviral vectors). In other cases (e.g. use of liposome vectors or naked DNA), this process is less well understood. At a practical level, gene therapy protocols may entail one of three different strategies (Figure 14.3). 

Some 24 per cent of all gene therapy clinical trials undertaken to date have employed retroviral vectors as gene delivery systems. Retroviruses are enveloped viruses. Their genome consists of ssRNA of approximately 5-8 kb. Upon entry into sensitive cells, the viral RNA is reverse transcribed and eventually yields double-stranded DNA. This subsequently integrates into the host cell genome (Box 14.1). The basic retroviral genome contains a minimum of three structural genes ... 

Figure 14.4 Schematic representation of (a) the proviral genome of a basic retrovirus and (b) the genome of a basic engineered retroviral vector carrying the gene of interest. Refer to text for further details...

Assembled retroviral vectors harboring the target gene which exit the cell... 

Repeat length, of fiber polymers, 11 175 Replication-defective retroviral vectors, 12 457... 

Vector Producer Cells. The direct administration of retroviral vector producer cells (e.g., murine cells producing HTK vector) to patients. 

Retroviral vector RNA from a virus that is used to insert genetic material into cells. [NIH]... 

Anson DS. The use of retroviral vectors for gene therapy - what are the risks A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery. Genet Vaccines Ther 2004 2. 

Keywords CD34 bone marrow transplantation retroviral vector insertional mntagenesis... 

Figure 1. Experimental Set up. Irradiated female mice were transplanted with retrovirally transduced BM cells from male donors (6 mice per vector). After 6 months of monitoring a secondary BMT took place. Spleen cells were used for the analysis of retroviral vector insertion sites (RVIS) by means of Ligation Mediated PCR (LM PCR) °. After another 6 months follow up spleen cells of the secondary recipients were again analysed for RVIS via LM-PCR.

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