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Biology Articles » Biochemistry » Nucleic Acid Biochemistry » Unregulated Hazards ‘Naked’ and ‘Free’ Nucleic Acids » Hazards of naked nucleic acids

Hazards of naked nucleic acids
- Unregulated Hazards ‘Naked’ and ‘Free’ Nucleic Acids

One of the key findings is that naked viral DNA is more infectious and have a wider host range than the intact virus. Human T-cell leukaemia viral DNA formed complete viruses when injected into the bloodstream of rabbits [34]. Similarly, naked DNA from the human polyomavirus BK (BKV) gave a full-blown infection when injected into rabbits, despite the fact that the intact BKV virus is not infectious [35]. This hazard is particularly relevant to the entire range of virus-based gene therapy vectors and naked DNA vaccines under development [36]. Modifications to viral genomes can have unexpected effects on virulence and the host range [37].

The safety of gene therapy vectors is unproven [38]. The hazards include both direct toxicities and indirect effects (see Box 3) and there is a growing debate over the potential for generating infectious viruses, and harmful effects due to random insertion into the cellular genome [39], both of which are shared by naked DNA vaccines. Recombinant DNA vaccines, in both the naked and intact viral form, also tend to be more unstable and prone to recombination, increasing the likelihood of generating new viruses [40]. A viral vaccine made by deleting genes from the simian immuno-deficiency virus (SIV) was found to cause AIDS in infant and adult macaques [41], raising serious safety concerns over similar AIDS viral vaccines for humans.

Gene therapy vectors and naked DNA vaccines can cause acute toxic shock reactions [42] and severe delayed immunological reactions [43]. Between 1998 and 1999, scientists from US drug companies failed to notify the FDA about six deaths that had occurred during clinical trials of gene therapy, the causes of which are yet to be determined [44]. Naked DNA can also trigger autoimmune reactions, in which the body’s immune system attack and kill its own tissues and cells. New research shows that any fragment of double-stranded DNA or RNA introduced into cells can induce these reactions which are responsible for many diseases [45]. Examples of autoimmune diseases are rheumatoid arthritis, insulin-dependent diabetes and Graves disease of the thyroid. Many ‘spontaneous mutations’ are due to insertions of transposable elements and other invasive DNA. Insertion mutagenesis is now found to be associated with a range of cancers, including lung [46], breast [47], colon [48] and liver [49] cancers. Finally, unintended modification of germ-cells may result from gene therapy and vaccinations [50].

Not as much is known concerning naked RNA. It is to be expected that antisense RNA, like antisense DNA, will have biological effects either in blocking the function of homologous genes or genes with homologous domains. RNA may also be reverse transcribed into complementary DNA (cDNA) by reverse transcriptase, which is present in all higher organisms as well as some bacteria [51], to become incorporated into the cell’s genome.

The direct uptake and incorporation of genetic material from unrelated species is referred to as horizontal gene transfer, or gene transfer by infection, to distinguish it from the usual vertical gene transfer from parent to offspring in reproduction.

 


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