Modulation of adenovirus infection in vitro by antisense oligodeoxynucleotides

Objective: Antisense oligodeoxynucleotides (ODNs) may represent a novel, airway directed approach to the treatment of adenovirus infection of the lung, for which no specific therapy exists. This study assessed the efficacy of antisense ODNs in modulating adenovirus infection in vitro. Methodology: A biological assay, which quantified viral plaque formation by wild type adenovirus 5 in a lung epithelial cell line (A549), was used to evaluate the inhibitory effect of a number of antisense ODNs targeted to the early (E) 1A and protein IX genes of adenovirus 5. Antisense ODNs (20-21mers, phosphorothioate end-protected) were designed to straddle the initiation of translation (AUG) codon of the mRNA of the targeted gene. Results: There was a consistent and significant (P < 0.005) reduction in viral plaque formation in those cells treated with an E1A antisense ODN, compared with the nonsense control ODN. Neither the addition of a cationic lipid (Lipofectamine), nor increasing the concentration of ODN from 1 mumol to 15 mumol enhanced the original inhibitory effect observed with the E1A antisense ODN. Conclusions: An antisense ODN targeted to the E1A gene can specifically inhibit adenovirus 5 infection in vitro, suggesting a potential therapeutic role for antisense ODNs in adenovirus infection of the lung.