Gene therapy with naked DNA: Potential steps towards deregulation

Research reports | 26.10.2010 | CGM 2010-06

Naked DNA or plasmid DNA (defined in this report as pDNA administered via a non-viral method) is frequently used as vector in DNA vaccination and gene therapy applications. Plasmid is a ring of extrachromosomal DNA, which can normally be found in bacteria. By using recombinant DNA techniques a gene of interest, the so-called insert, can be introduced in the plasmid. In order to obtain expression of this insert in eukaryotic cells, plasmids contain promoter and polyadenylation sequences.  In addition, an “origin of replication” and often an antibiotic resistance sequence are inserted in the plasmid backbone to induce replication in the production cell E.coli and to allow selection for retention. Naked DNA has a hypothetical environmental risk, which includes the risk for the creation and spreading of new genetically modified organisms (gmo’s). In theory, new gmo’s can be created upon the uptake of naked DNA by somatic cells, germ line cells, viruses or bacteria. The previous COGEM report from 2004 showed that the environmental risk of naked DNA is minimal. In this report COGEM advised to divide naked DNA vectors for the use in humans into three categories, based on their environmental risk. This study functioned as starting platform for the current report. In the past years, several strategies to improve the low transfection efficiency of naked DNA compared to viral vectors have been published. This research can be divided into the design of 1.) improved expression vectors, 2.) synthetic carrier systems and 3.) physical and mechanical delivery techniques.
In this report, the current environmental risk of naked DNA is reevaluated and the effect of new developments on the potential environmental risk is assessed.

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