Efficient transfer of genes into senescent cells by adenovirus vectors via highly expressed alpha v beta 5 integrin.

Although various methods for transferring genes into mammalian cells have been established, none have been successful with senescent cells. In this report, we present evidence of the efficient transfer of a gene into human senescent fibroblasts using an adenoviral vector. By employing a recombinant adenovirus vector harboring the beta-galactosidase gene (Ad-CAG beta NR), we observed a good correlation between the proportion of beta-galactosidase positive cells and population doubling of the infected cells. In addition, 1.5- to 6.0-fold greater beta-galactosidase activity was observed in senescent fibroblasts (population doubling [PD] = 58) than in young cells (PD = 15). Western blotting analysis revealed that, compared with young fibroblasts, senescent fibroblasts expressed larger amounts of alpha v beta 5 and alpha v beta 3 integrins which were thought to form part of the adenovirus receptor. These results suggest that higher expression of alpha v beta 5 and alpha v beta 3 integrins in senescent cells renders them more sensitive to adenovirus infection than young cells. Thus, adenovirus vectors may prove to be useful in gene therapy strategies directed against senescence-related disorders.