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Biology Articles » Biochemistry » Nucleic Acid Biochemistry » Unregulated Hazards ‘Naked’ and ‘Free’ Nucleic Acids » DNA persists in all environments and is readily taken up by cells of all organisms

DNA persists in all environments and is readily taken up by cells of all organisms
- Unregulated Hazards ‘Naked’ and ‘Free’ Nucleic Acids

Naked or free DNA are now known to persist in all natural environments, and high concentrations are found in the soil, in marine and fresh water sediments as well as in the air-water interface, where it retains the ability to transform microorganisms [14]. DNA also persists in the mouth [15] and the digestive tract of mammals [16], where it may be taken up and incorporated by the resident microbes, and by the cells of the mammalian host.

A genetically engineered plasmid was found to have a 6 to 25% survival after 60 min. of exposure to human saliva. The partially degraded plasmid DNA was capable of transforming Streptococcus gordonii, one of the bacteria that normally live in the human mouth and pharynx. Human saliva contains factors that promote competence of resident bacteria to become transformed by DNA [17].

It has long been assumed that DNA cannot be taken up through intact skin, surface wounds, or the intestinal tract, or that it would be rapidly destroyed if taken up. Those assumptions have been overtaken by empirical findings. The ability of naked DNA to penetrate intact skin has been known at least since 1990. Cancer researchers found that within weeks of applying the cloned DNA of a human oncogene to the skin on the back of mice, tumours developed in endothelial cells lining the blood vessel and lymph nodes [18].

Viral DNA fed to mice is found to reach white blood cells, spleen and liver cells via the intestinal wall, to become incorporated into the mouse cell genome [19]. When fed to pregnant mice, the viral DNA ends up in cells of the fetuses and the new born animals, suggesting that it has gone through the placenta as well [20]. The authors remark that "The consequences of foreign DNA uptake for mutagenesis and oncogenesis have not yet been investigated." [21]

Recent developments in gene therapy demonstrate how readily naked nucleic acids (see Table 2) can gain access to practically every type of human cells and cells of model mammals. Naked nucleic acids can be successfully delivered, either alone or in complex with liposomes and other carriers, in aerosols via the respiratory tract [22], by topical application to the eye [23], to the inner ear [24], via hair follicles [25], direct injection into muscle [26], through the skin [27], as well as by mouth, where the nucleic acid is taken up by cells lining the gut [28]. Naked DNA can even be taken up by sperm cells of marine organisms and mammals, and transgenic animals created [29]. Geneticists are contemplating using sperms as vectors in gene therapy.

High levels of foreign gene expression was observed in the liver cells of rats, mice and dogs when naked DNA was injected into blood vessels supplying the liver [30]. Gene expression is observed in skin cells injected with naked DNA [31], and naked DNA was integrated into chromosomes of cells and expressed in human and pig skin [32]. Researchers have found integration of a plasmid-based naked DNA malarial vaccine injected into mouse muscle in a preclinical trial, but dismissed it as "3000 times less than the spontaneous mutation rate for mammalian genome" and hence "not considered to pose a significant safety concern" [33].

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