ADENOVIRUS-MEDIATED GENE-TRANSFER

The introduction of foreign genetic material into somatic cells in intact organisms is an important investigational technique that holds considerable promise as a therapeutic tool. Although successful gene transfer has been achieved by the use of both cell-mediated and direct techniques, most strategies have been limited either by constraints on the type, accessibility, and growth state of the target cell population, or by the low efficiency of genetic modification. Among the available vectors for somatic cell gene transfer, recombinant adenoviruses have several properties that make them particularly attractive for direct, in vivo introduction of foreign genes into adult animals and people. Simple techniques for the efficient generation and propagation of recombinant adenoviruses have been developed, and early studies employing recombinant adenoviral vectors demonstrate their potential for broad experimental and eventual clinical application. To exploit this potential properly, a number of important issues, including the efficiency of genetic modification of a targeted cell population, stability of foreign gene expression, effects of host immune response, and cell-type specific targeting of gene transfer, remain to be addressed.