Overview of biological effects of addition of DNA molecules to cells

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Abstract
Injected DNA proceeds with certain probabilities through the following steps: degradation by serum nucleases, adsorption to cells, uptake into cells, ligation to other DNA, mutation, expression of unintegrated DNA, integration, expression of integrated DNA, and activation of or inactivation of cellular genes. The maximal probability per DNA molecule of each of these steps is estimated based on experimental results in cell culture with transfection of DNA and with infection by retroviruses. A maximum cumulative probability of having a harmful effect is calculated to be less than 10−16 to 10−19 per DNA molecule from a cell without activated proto‐oncogenes or active viral oncogenes. The most frequent harmful effects considered are inactivation of a tumor suppressor gene and activation of a proto‐oncogene. Such inactivation and activation in a cell that could give rise to cancer would increase the age‐standardized incidence of cancer by a small amount. The amount of increase would differ among individuals depending upon their genotypes and their environments. Thus, the magnitude of the increase will depend upon the frequency of more sensitive individuals. The probability of an increased incidence of cancer as a possible effect of the vaccination should be compared to the number of DNA molecules to be injected per person and to the protective effects of a successful HBV vaccine.