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 h ave been established, none have been successful with senescent cells. In this report, we present evidence of the efficient transfer of a gen e into human senescent fibroblasts using an adenoviral vector. By empl oying a recombinant adenovirus vector harboring the beta-galactosidase gene (AdCAG beta NR), we observed a good correlation between the prop ortion of beta-galactosidase positive cells and population doubling of the infected cells. In addition, 1.5- to 6.0-fold greater beta-galact osidase activity was observed in senescent fibroblasts (population dou bling [PD] = 58) than in young cells (PD=15). Western blotting analysi s revealed that, compared with young fibroblasts, senescent fibroblast s expressed larger amounts of alpha v beta 5 and alpha v beta 3 integr ins which were thought to form part of the adenovirus receptor. These results suggest that higher expression of alpha v beta 5 and alpha v b eta 3 integrins in senescent cells renders them more sensitive to aden ovirus infection than young cells. Thus, adenovirus vectors may prove to be useful in gene therapy strategies directed against senescence-re lated disorders. (C) 1997 Academic Press.