[Significance of recombinant adenoviruses in experimental gene therapy]

In the past few years recombinant adenoviruses have emerged as promising technology in the gene therapy. They have been used for genetic modification of a variety of somatic cells in vitro and in vivo. They offer several advantages over other vectors. Replication defective vectors can be produced in very high titers (10(11) pfu/ml) thus allowing a substantially greater efficiency of direct gene transfer, they have the capacity to infect both replicating and nonreplicating cells, and the DNA functions in an extrachromosomal fashion, which eliminates the risk of insertional mutagenesis. Several important limitations of adenovirus-mediated gene transfer are also known, such as the relatively short term expression of foreign genes, the dose-related direct toxic effect, and that the host immune response to the viral proteins may substantially inhibit the effect of repeated infection with recombinant adenoviruses. Recombinant adenoviruses of types 2 and 5 are used most frequently as vectors for direct gene transfer. The author's experiments with monoclonal antibodies raised against the adenovirus hexon proteins revealed the existence of a remarkable homogeneity in the antigenic structure among the hexon types of subgenus C (types 1, 2, 5 and 6). Besides the genus and type specific epitopes the presence of at least 15 identical intertype specific epitopes were demonstrated on the surface of the hexons. The data suggest that recombinant adenoviruses constructed from the types of subgenus C cannot be replaced by each other to avoid the host immune response in repeated infections in gene therapy because of their close antigens relationships.