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Genetic Engineering and Site‐Specific Mutagenesis

One of the ultimate goals of genetic engineering is to correct damage in vitally important genes. It should hardly be called into question that in the near future geneticists will develop a method of introducing the product of genetic engineering into a damaged organism to replace a damaged gene. On the other hand, the success in the chemical analysis of the structure of polynucleotides' and polypeptides allows one to present a general scheme of analysis of the defects in definite sites of many damaged genes of different organisms (FIGURE 1 ) . Together with genetic engineering, essential aid in the correction of hereditary lesions might be received from the development of a new method of genetic manipulation, namely, directed and site-specific mutagenesis. Even until recently geneticists believed that directed mutagenesis, i.e., the induction of mutations into predetermined genes without influence on other genes of the organism, could hardly be possible in the foreseeable future (see Reference 2). Today this problem can be considered as essential and solvable. Some authors managed to realize the mutagenesis of selected groups of genes or even definite sites inside genes on the model of short segments of DNA (phage, plasmid, etc.)."" The first attempt has been made to induce mutations in bacteriophage T7 during its propagation in Escherichia coli cells, i.e., in the simplest in vivo system." However, none of these works touch upon the possibility of real mutagenesis in vivo. Nevertheless, it seems possible to propose a method of strictly site-specific and directed mutagenesis of both individual cells and, perhaps, organisms. In the present communication we discuss the basis of directed site-specific mutagenesis, suggest a theoretical model of induction of point mutations and short deletions and insertions in any supposed sites (or segments) of the genes, and examine the possibility of the simultaneous and complementary implementation of this method and genetic engineering.