Gene therapy of mass pathologies

DNA recombinant molecules carrying different allels of human preproinsulin gene as mutagens in Chinese hamster cells

“…These results confirm the idea that the functional activity of recombinant DNAs and particularly transgenes plays an important role in induction of mutagenesis. The expression of exogenous preproinsulin gene (allel-1) included into the pBR322ins recombinant plasmid in cultivated fibroblasts of different origin have been shown [12,13]. At the present time we have no comparative data on the expression of two studied allels of the human preproinsulin gene in Chinese hamster cells.…”

“…We focus our attention on a mutagenic potential of recombinant DNAs and influence of introduced genes on a variety of methabolic pathways involving activation of proto-oncogenes as well [2]. This concerns especially anti-diabet strategy using recombinant adenovirus [24,25] and plasmids containing the preproinsulin gene [13].…”

“…1 and 2). Intracellular expression of the human preproinsulin gene included into the plasmid vectors was demonstrated after introduction into fibroblasts of different origin in our earlier investigations [13]. The pBR322insN plasmid carrying the frameshift mutation in the region of initiation of the translation of the human preproinsulin gene was also constructed in our Institute (Fig.…”

“…Recombinant plasmids containing human preproinsulin gene (pBR322ins and pAins) has been shown to induce gene mutations and chromosomal aberrations in the same cells as well [8][9][10][11]. The preproinsulin gene (allel-1) was able to function in different cell types under its own promoter since it lacked a regulatory element providing a tissue-specific expression [12,13].Introduction of a frameshift mutation into the region of initiation of the translation of the transgene (allel-2) diminished the mutagenic effect of the corresponding recombinant plasmid (pBR322insN) on gene level [10].…”

Regulation of mutagenesis by exogenous biological factors in the eukaryotic cell systems

“…It is the International agency on research of cancerogenic risk in the World Health Organization (WHO), which concluded that food is a source of a complex mix of mutagens and carcinogens of different nature [34]. An application of genetically modified food and recombinant DNAs on the basis of virus vectors and human cells as pharmaceutical preparations for gene and cell therapy, poses a problem of genetic consequences of alien biological factors introduced into a human body [35][36][37].…”