Gene therapy plasmid-based vectors

Presently, 1,260 gene-therapy trials are underway worldwide (Tables 1 and 2). For details see http // www.wiley.co.uk/genetherapy/clinical/. Almost three fourths of all trials are based on viral vectors. The vast majority of nonviral gene-therapy trials use naked/ plasmid DNA (18% of all gene-therapy trials). 

The system used to deliver the desired gene into the cells, called the gene therapy vector, may be a virus, a plasmid, or even just the naked DNA. The choice of vector is based on the difficulty of getting the gene into the cell, the amount of DNA the vector can carry, the size of the gene sequence needed to provide the correct protein, and the effects the vector may have on the body. Each type of vector has advantages and disadvantages. 

Maruyama-Tabata FI, et al. (2000). Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer. Gene Ther. 7 53-60. Wang Y, et al. (2001). Combination of electroporation and DNA/dendrimer complexes enhances gene transfer into murine cardiac transplants. Am. J. Transplant. 1 334-338. 

Compared to 66.5% of gene therapy clinical trials aiming at the treatment of cancer, only 2 of the 12 siRNA clinical trials are designed for cancer therapy, indicating the siRNA cancer therapy is still in its infancy. Same as the therapeutic application of pDNA, the major bottleneck for a successful siRNA therapy is the efficient delivery. Scientists have gained extensive experiences in the delivery of pDNA and these experiences can be utilized for the delivery of plasmid-based shRNA. However, the same experience cannot be transferred to siRNA directly since siRNA is very different from pDNA in terms of the molecular weight, molecular topography, and in vivo stability. In addition, compared to pDNA, siRNA is more difficult to be condensed into nanosized complex. Nevertheless, many nonviral vectors have been developed for siRNA delivery and one of them was recently approved for phase I clinical trial. 

Maruyama-Tabata, H. et al.. Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer. Gene Ther., 7, 53,2000. 

The rAAV vectors have theoretical advantages as vehicles for human gene therapy, because they are based on a virus that is nonpathogenic and has a natural mechanism for long-term persistence in human cells (16-18). rAAV vectors were prepared by generating proviral rAAV vector plasmids deleted for the viral pro-... 

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